How to treat intestinal infections

Abstract

The present invention relates to compositions and methods for treating or preventing infectious diseases, particularly infections caused by intracellular parasites such as Cryptosporidium species. The present invention also relates to compositions and methods for treating or preventing viral or bacterial infections, particularly intestinal infections such as those caused by rotavirus and Salmonella species infections. The methods include administering a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor, such as lapaquistat, and the composition includes a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor, such as lapaquistat.

Description

[Technical Field]

[0001] The present invention relates to compositions and methods for treating clinical conditions resulting from intestinal infections, particularly parasitic diseases such as those caused by Cryptosporidium species. The present invention also relates to compositions and methods for treating clinical conditions resulting from intestinal diseases, such as viral and bacterial infections, particularly those caused by rotavirus and Salmonella species infections. [Background technology]

[0002] Cryptosporidium parasites are a major cause of diarrheal disease in humans and livestock. In humans, immunocompromised patients and children bear a substantial burden of disease. The only approved drug for human use, nitazoxanide, has limited efficacy in malnourished and immunocompromised patients.[1] Complications from Cryptosporidium infection result in 50,000 to 200,000 deaths per year, primarily among children, with a strong correlation between cases in younger age groups and chronic malnutrition.[2] No vaccine is available, and more effective therapies to treat infection are desperately needed.

[0003] Cryptosporidium is a eukaryotic pathogen that specifically infects epithelial cells within the host intestine. As an intracellular parasite, Cryptosporidium is completely dependent on host cells for nutrients and shelter during growth and replication. Parasite replication occurs both asexually (mitotically) and sexually (meiotically), the latter being required for the production of new follicles, the infectious form of the parasite. To identify host genes and pathways essential for supporting parasite growth and development, we used a high-throughput, microscopy-based CRISPR screen across the entire human genome. From this screen, we identified the host gene FDFT1, or farnesyl diphosphate farnesyltransferase 1, as essential for parasite growth and development. Furthermore, we identified two FDFT1 inhibitors, TAK-475 or lapaquistat, and YM-53601, that can block Cryptosporidium growth and development. Lapaquistat is described in detail in US6613761B1, which is incorporated herein by reference. YM-53601 is described in detail in document [3], which is incorporated herein by reference. Summary of the Invention

[0004] The present invention provides a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor, or a pharmaceutically acceptable salt thereof, for use in a method for treating or preventing an infectious disease. In some embodiments, the infectious disease is caused by an intracellular pathogen incapable of endogenous cholesterol biosynthesis. In some embodiments, the infectious disease is caused by an intracellular pathogen incapable of endogenous squalene synthesis. In some embodiments, the infectious disease is caused by an intracellular pathogen that does not express endogenous squalene synthase.

[0005] The present invention provides a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor, or a pharmaceutically acceptable salt thereof, for use in a method of treating or preventing a parasitic infection.

[0006] The present inventors have surprisingly found that effective inhibition of parasite growth can be achieved by targeting the host's cholesterol biosynthesis pathway (as opposed to cholesterol biosynthesis in the parasite), particularly by inhibiting FDFT1 (squalene synthase) activity. Lapaquistat is a suitable FDFT1 inhibitor that can be used to treat parasitic infections (e.g., Cryptosporidium infections) according to the methods of the present invention, as shown, for example, in Example 3. Because of its unique mechanism of action, FDFT1 inhibition is also expected to be an effective treatment for other pathogens that depend on host cells for cholesterol biosynthesis, particularly other intracellular pathogens that depend on host cells for cholesterol biosynthesis.

[0007] In some embodiments, the parasitic infection is an infection by an intracellular parasite that is incapable of endogenous cholesterol biosynthesis. In some embodiments, the parasitic infection is an infection by an intracellular parasite that is incapable of endogenous squalene synthesis. In some embodiments, the parasitic infection is an infection by an intracellular parasite that does not express endogenous squalene synthase. In some embodiments, the parasitic infection is an infection by an intracellular parasite that is an obligate intracellular parasite.

[0008] In some embodiments, the parasitic infection is an infection with an intracellular parasite of the order Eucoccidiorida, preferably the suborder Eimeriorina. Preferably, the parasite is a Cryptosporidium species.

[0009] The present invention also provides a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor, or a pharmaceutically acceptable salt thereof, for use in a method of treating or preventing a Cryptosporidium infection.

[0010] The present invention also provides a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof for use in a method for treating or preventing a viral infection. In some embodiments, the viral infection is an infection caused by an enveloped virus. Because viruses are intracellular pathogens incapable of endogenous cholesterol biosynthesis, FDFT1 inhibition is expected to be effective in treating viral infections, particularly enveloped viruses that depend on host cell cholesterol biosynthesis.

[0011] The present invention also provides a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor, or a pharmaceutically acceptable salt thereof, for use in a method for treating or preventing a rotavirus infection.

[0012] The present invention also provides a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof for use in a method for treating or preventing a bacterial infection. In some embodiments, the bacterial infection is an infection caused by an intracellular bacterium incapable of endogenous cholesterol biosynthesis. In some embodiments, the bacterial infection is an infection caused by an intracellular bacterium incapable of endogenous squalene synthesis. In some embodiments, the bacterial infection is an infection caused by an intracellular bacterium that does not express endogenous squalene synthase.

[0013] The present invention also provides a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor, or a pharmaceutically acceptable salt thereof, for use in a method of treating or preventing a Salmonella infection.

[0014] In some embodiments, the FDFT1 inhibitor is lapaquistat or a pharmaceutically acceptable salt thereof. In some embodiments, the FDFT1 inhibitor has the following structure: [ka]

[0015] In some embodiments, the FDFT1 inhibitor is lapaquistat.

[0016] In some embodiments, the FDFT1 inhibitor is YM53601 or a pharmaceutically acceptable salt thereof. In some embodiments, the FDFT1 inhibitor has the following structure: [ka]

[0017] In some embodiments, the FDFT1 inhibitor is administered simultaneously, sequentially, or separately with one or more other drugs used in the treatment or prevention of a parasitic infection or a Cryptosporidium infection, in some embodiments, the one or more other drugs are formulated in a combined preparation with the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof.

[0018] In some embodiments, the one or more other drugs include nitazoxanide, paromomycin, or halofuginone. In some embodiments, the one or more other drugs include nitazoxanide.

[0019] The present inventors have surprisingly found that combining a FDFT1 inhibitor (e.g., lapaquistat) with a statin (e.g., lovastatin or atorvastatin) synergistically improves inhibition of parasite growth, as described in Example 5. Thus, in some embodiments, a FDFT1 inhibitor is administered simultaneously, sequentially, or separately with one or more other drugs that inhibit cholesterol biosynthesis and / or reduce the amount of cholesterol in the subject's blood. In some embodiments, the one or more other drugs that inhibit cholesterol biosynthesis and / or reduce the amount of cholesterol in the subject's blood are statins. In some embodiments, the statin is selected from one or more of lovastatin, atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin. In some embodiments, the statin is lovastatin or atorvastatin.

[0020] In some embodiments, the FDFT1 inhibitor is lapaquistat, and the lapaquistat is administered simultaneously, sequentially, or separately from the lovastatin or atorvastatin.

[0021] The present invention also provides a statin for use in a method for treating or preventing an infection, wherein the statin is administered simultaneously, sequentially, or separately from the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof.

[0022] The present invention provides a combination of a FDFT1 inhibitor or a pharmaceutically acceptable salt thereof with a drug that inhibits cholesterol biosynthesis and / or reduces the amount of cholesterol in a subject's blood. This combination may be for use in a method for treating or preventing an infectious disease. In some embodiments, the infectious disease is caused by an intracellular pathogen that is incapable of endogenous cholesterol biosynthesis. In some embodiments, the infectious disease is caused by an intracellular pathogen that is incapable of endogenous squalene synthesis. In some embodiments, the infectious disease is caused by an intracellular pathogen that does not express endogenous squalene synthase. The infectious disease may be an intracellular parasitic, viral, or bacterial infection. The infectious disease may preferably be an intracellular parasitic infection. The infectious disease may be a Cryptosporidium infection, a rotavirus infection, or a Salmonella infection. The infectious disease may preferably be caused by a Cryptosporidium infection. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof may be lapaquistat or YM53601. The drug that inhibits cholesterol biosynthesis and / or reduces the amount of cholesterol in the subject's blood can be a statin, such as a statin selected from the group consisting of lovastatin, atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin. In some preferred embodiments, the statin is lovastatin or atorvastatin.

[0023] In embodiments relating to a combination of a FDFT1 inhibitor or a pharmaceutically acceptable salt thereof with a drug that inhibits cholesterol biosynthesis and / or reduces the amount of cholesterol in a subject's blood, the two components may be administered simultaneously, sequentially, or separately. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof may be lapaquistat or YM53601. The drug that inhibits cholesterol biosynthesis and / or reduces the amount of cholesterol in a subject's blood may be a statin, such as a statin selected from the group consisting of lovastatin, atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin. In some preferred embodiments, the statin is lovastatin or atorvastatin.

[0024] Other combinations are also contemplated. For example, in the case of parasitic infections, a FDFT1 inhibitor or a pharmaceutically acceptable salt thereof can be combined with one or more other drugs used in the treatment or prevention of parasitic infections, such as Cryptosporidium infections. Such drugs can be nitazoxanide, paromomycin, or halofuginone. In some embodiments, the additional drug is a triple combination of nitazoxanide, a FDFT1 inhibitor or a pharmaceutically acceptable salt thereof, and a drug that inhibits cholesterol biosynthesis and / or reduces the amount of cholesterol in the subject's blood (such as a statin), as well as one or more other drugs used in the treatment or prevention of Cryptosporidium infections (such as nitazoxanide, paromomycin, or halofuginone). The components of any combination can be for simultaneous, separate, or sequential administration.

[0025] Also provided is a composition comprising an FDFT1 inhibitor or a pharmaceutically acceptable salt thereof and a drug that inhibits cholesterol biosynthesis and / or reduces the amount of cholesterol in a subject's blood. The composition may be for use in a method for treating or preventing an infectious disease. In some embodiments, the infectious disease is caused by an intracellular pathogen incapable of endogenous cholesterol biosynthesis. In some embodiments, the infectious disease is caused by an intracellular pathogen incapable of endogenous squalene synthesis. In some embodiments, the infectious disease is caused by an intracellular pathogen that does not express endogenous squalene synthase. The infectious disease may be an intracellular parasitic, viral, or bacterial infection. The infectious disease may preferably be an intracellular parasitic infection. The infectious disease may be a Cryptosporidium infection, a rotavirus infection, or a Salmonella infection. The infectious disease may preferably be caused by a Cryptosporidium infection. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof may be lapaquistat or YM53601. The drug that inhibits cholesterol biosynthesis and / or reduces the amount of cholesterol in the subject's blood can be a statin, such as a statin selected from the group consisting of lovastatin, atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin. In some preferred embodiments, the statin is lovastatin or atorvastatin. The composition can further include one or more other drugs used in the treatment or prevention of parasitic infections, such as Cryptosporidium infections. Such drugs can be nitazoxanide, paromomycin, or halofuginone.

[0026] Also provided is a kit of parts comprising a FDFT1 inhibitor or a pharmaceutically acceptable salt thereof and a drug that inhibits cholesterol biosynthesis and / or reduces the amount of cholesterol in a subject's blood. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof and the drug that inhibits cholesterol biosynthesis and / or reduces the amount of cholesterol in a subject's blood may be separately disposed in separate containers. The kit of parts may further include instructions for use. For example, the instructions may be for treating or preventing an infectious disease. In some embodiments, the infectious disease is an infection caused by an intracellular pathogen incapable of endogenous cholesterol biosynthesis. In some embodiments, the infectious disease is an infection caused by an intracellular pathogen incapable of endogenous squalene synthesis. In some embodiments, the infectious disease is an infection caused by an intracellular pathogen that does not express endogenous squalene synthase. The infectious disease may be an intracellular parasitic, viral, or bacterial infection. The infectious disease may preferably be an intracellular parasitic infection. The infectious disease may be a Cryptosporidium infection, a rotavirus infection, or a Salmonella infection. The infection may preferably be caused by a Cryptosporidium infection. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof may be lapaquistat or YM53601. The drug that inhibits cholesterol biosynthesis and / or reduces the amount of cholesterol in the subject's blood may be a statin, such as a statin selected from the group consisting of lovastatin, atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin. In some preferred embodiments, the statin is lovastatin or atorvastatin. The kit may further include one or more other drugs used in the treatment or prevention of parasitic infections, such as Cryptosporidium infections. Such drugs may be nitazoxanide, paromomycin, or halofuginone.

[0027] In some embodiments, the FDFT1 inhibitor is administered to a patient orally, intravenously, intramuscularly, intrathecally, subcutaneously, sublingually, bucally, rectally, vaginally, ophthalmically, otorally, nasally, by inhalation, by spray, dermally, topically, or transdermally. In some embodiments, the subject is a human. In some embodiments, the subject is a cow (cattle), sheep, goat, cat, dog, pig (swine), horse, or rabbit.

[0028] In some embodiments, the FDFT1 inhibitor is administered at a dose sufficient to achieve at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99% inhibition of FDFT1 activity. In some embodiments, the FDFT1 inhibitor is administered at a dose sufficient to achieve at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99% inhibition of squalene production in target cells. In some embodiments, the FDFT1 inhibitor prevents sexual development of the parasite. In some embodiments, the FDFT1 inhibitor reduces parasite reproduction.

[0029] In some embodiments, the method comprises administering to the patient a FDFT1 inhibitor or a pharmaceutically acceptable salt thereof at a dose of 0.0001 mg / kg to 100 mg / kg, hi some embodiments, the method comprises administering to the patient a FDFT1 inhibitor or a pharmaceutically acceptable salt thereof at a dose of 25 mg to 100 mg once daily.

[0030] The present invention also provides the use of a therapeutically or prophylactically effective amount of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof in a method for treating or preventing a parasitic infection.

[0031] The present invention also provides the use of a therapeutically or prophylactically effective amount of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor, or a pharmaceutically acceptable salt thereof, in a method for treating or preventing a Cryptosporidium infection.

[0032] Lapaquistat already has substantial human safety data (over three large-scale clinical trials). There is strong potential for repurposing lapaquistat for the treatment of parasitic diseases, specifically Cryptosporidium treatment. Cryptosporidium treatment does not require chronic administration, and because lapaquistat has low bioavailability, it is believed that the drug will concentrate at the site of intestinal infection, increasing its efficacy and allowing for the use of lower doses.

[0033] The infectious diseases treated by the present invention can be intracellular infections, i.e., infections caused by intracellular pathogens. In such infections, the pathogen typically uses host cellular mechanisms to enter, replicate, propagate, and spread within the host cell. This is in contrast to extracellular infections, in which the pathogen remains outside the host cell. [Brief explanation of the drawings]

[0034] [Figure 1] FDFT1 inhibition as a treatment for Cryptosporidium infection. A) Schema of a microscopy-based genome-wide CRISPR-Cas9 screen to identify host factors essential for Cryptosporidium parasite growth and development. B) Median z-scores from three biological replicates. Note that FDFT1 is highly significant in reducing total parasite numbers (left—total parasites / total host nuclei) and is identified as the highest z-score in reducing parasite development (right—total female parasites / total parasites). C) Lapaquistat treatment of infected intestinal epithelial cells demonstrates efficacy against parasite growth and development, as measured by the % female parasites among the total parasites identified. [Figure 2]FDFT1 inhibition by YM-53601 as a treatment for Cryptosporidium. YM-53601 treatment of infected intestinal epithelial cells shows efficacy against parasite growth and development, as measured by % female parasites among total parasites identified. [Figure 3] Synergistic combination of FDFT1 inhibition and statins. Intestinal epithelial cells (HCT-8) were infected with Cryptosporidium parasites and treated with increasing concentrations of lapaquistat acetate or lovastatin, either alone or in combination. The efficacy of lapaquistat in limiting Cryptosporidium growth was synergistically increased when combined with lovastatin. DETAILED DESCRIPTION OF THE INVENTION

[0035] definition The following provides specific definitions of terms, technical means, and embodiments used in this specification.

[0036] As used herein, the term "approximately" or "about," when applied to one or more values ​​of interest, refers to a value similar to a stated reference value. In some embodiments, the term "approximately" or "about," unless otherwise stated or clear from the context, refers to a range of values ​​that falls within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction (greater or less) of the stated reference value (except where such number would exceed 100% of possible values).

[0037] As used herein, the term "amelioration" refers to the prevention, reduction, or alleviation of a condition, or an improvement in a subject's condition or disease biomarkers of severity or outcome. Amelioration includes, but is not required to include, complete reversal or complete prevention of the disease state.

[0038] As used herein, the term "comparable" refers to a system, set of conditions, effect, or result that is sufficiently similar to a test system, set of conditions, effect, or result to allow a scientifically valid comparison. Those skilled in the art will recognize and understand which systems, sets of conditions, effects, or results are sufficiently similar to be "comparable" to any particular test system, set of conditions, effect, or result described herein.

[0039] The term "correlate" as used herein has its ordinary meaning of "exhibiting a correlation with." Those skilled in the art will understand that two features, items, or values ​​exhibit a correlation with one another when they show a tendency to appear and / or change together. In some embodiments, a correlation is statistically significant when its p-value is less than 0.05, and in some embodiments, a correlation is statistically significant when its p-value is less than 0.01. In some embodiments, the correlation is assessed by regression analysis. In some embodiments, the correlation is a correlation coefficient.

[0040] As used herein, the terms "improve," "increase," or "reduce," or grammatical equivalents, refer to a value relative to a reference (baseline) measurement, such as a measurement in the same individual prior to initiation of a treatment described herein (e.g., a measurement obtained under comparable conditions), or a measurement in a control individual (or control individuals) in the absence of a treatment described herein.

[0041] As used herein, a "polypeptide" generally refers to a chain of at least two amino acids linked together by peptide bonds. In some embodiments, a polypeptide may contain at least three to five amino acids linked to other amino acids by at least one peptide bond. Those skilled in the art will understand that polypeptides may, in some cases, include "unnatural" amino acids or other entities that may nevertheless be optionally incorporated into a polypeptide chain.

[0042] As used herein, the term "protein" refers to a polypeptide (i.e., a chain of at least two amino acids linked together by peptide bonds). A protein may contain moieties other than amino acids (e.g., may be a glycoprotein, proteoglycan, etc.) and / or may be otherwise processed or modified. Those of skill in the art will understand that a "protein" may be an entire polypeptide chain (with or without a signal sequence) produced by a cell, or a characteristic portion thereof. Those of skill in the art will understand that a protein may sometimes comprise two or more polypeptide chains, for example, linked by one or more disulfide bonds or associated by other means. Polypeptides may contain L-amino acids, D-amino acids, or both, and may contain any of a variety of amino acid modifications or analogs known in the art. Useful modifications include, for example, terminal acetylation, amidation, methylation, etc. In some embodiments, a protein may comprise natural amino acids, unnatural amino acids, synthetic amino acids, and combinations thereof. The term "peptide" is generally used to refer to a polypeptide having a length of less than about 100 amino acids, less than about 50 amino acids, less than 20 amino acids, or less than 10 amino acids.

[0043] As used herein, the terms "subject," "individual," or "patient" refer to any living organism to which embodiments of the present invention may be used or administered, e.g., for experimental, diagnostic, prophylactic, and / or therapeutic purposes. These terms include both mammals, such as humans, and domestic animals, such as laboratory animals and household pets (e.g., cats, dogs, pigs, cows, sheep, goats, horses, and rabbits), as well as non-domestic animals, such as wild animals. In exemplary aspects of the present invention, accepted screening methods are used to determine risk factors associated with the targeted or suspected disease or condition or to determine the status of an existing disease or condition in a subject to identify a subject patient for treatment with the methods of the present invention. These screening methods include, for example, conventional diagnostic techniques associated with the targeted or suspected disease or condition. These and other conventional methods allow clinicians to select patients in need of treatment using the methods and formulations of the present invention. In preferred embodiments of the present invention, the subject is a human. In some embodiments of the present invention, the subject is a domestic animal, such as a cat, dog, pig (pig), cow (bovine), sheep, goat, horse, or rabbit. In some embodiments of the invention, the subject is a bovine (cattle). In some embodiments of the invention, the subject is a sheep. In some embodiments of the invention, the subject is a goat. In some embodiments of the invention, the subject is a cat. In some embodiments of the invention, the subject is a dog. In some embodiments of the invention, the subject is a porcine (pig).

[0044] As used herein, the term "therapeutic regimen" refers to any method used to partially or completely alleviate, ameliorate, alleviate, inhibit, prevent, delay onset, reduce severity, and / or reduce incidence of one or more symptoms or characteristics of a particular disease, disorder, and / or condition. It may involve the administration of one or more doses, optionally spaced by regular or different time intervals. In some embodiments, a therapeutic regimen is one whose performance is designed to achieve and / or correlates with achieving a particular effect (e.g., reduction or elimination of a harmful condition or disease) (e.g., across a population of relevant cells, tissues, or organisms). In some embodiments, treatment involves the administration of one or more therapeutic agents simultaneously, sequentially, or at different times, at the same or different times. In some embodiments, a "therapeutic regimen" includes genetic methods such as gene therapy, gene disruption, or other methods known to induce or reduce expression (e.g., transcription, processing, and / or translation of a particular gene product, such as a primary transcript or mRNA).

[0045] As used herein, the term "therapeutically effective amount" refers to an amount of a therapeutic agent that confers a therapeutic effect on a treated subject at a reasonable benefit / risk ratio applicable to any medical treatment. Such a therapeutic effect can be objective (i.e., measurable by some test or marker) or subjective (i.e., the subject gives an indication of or feels an effect). In some embodiments, a "therapeutically effective amount" refers to an amount of a therapeutic agent or composition that is effective in treating, ameliorating, or preventing a particular disease or condition, or that exhibits a detectable therapeutic or preventative effect, such as by ameliorating symptoms associated with the disease, preventing or delaying the onset of the disease, and / or reducing the severity or frequency of symptoms of the disease. A therapeutically effective amount can typically be administered in a dosing regimen that can include multiple unit doses. For any particular therapeutic agent, the therapeutically effective amount (and / or appropriate unit dose within an effective dosing regimen) can vary depending, for example, on the route of administration or combination with other drugs. Alternatively, or additionally, the particular therapeutically effective amount (and / or unit dose) for any particular patient may depend on a variety of factors, including the activity of the particular therapeutic agent used; the particular composition used; the age, weight, general health, sex, and diet of the patient; the time of administration, route of administration, and / or rate of excretion or metabolism of the particular therapeutic agent used; duration of treatment; and similar factors well known in the medical arts. As used herein, the term "prophylactically effective amount" refers to the amount of agent needed to prevent a parasitic or infectious disease or disorder as defined elsewhere herein.

[0046] Preferably, the dose of the drug is sufficient to inhibit FDFT1 activity in the subject as much as possible. The dose of drug delivered can be, for example, about 1, 1.5, 2, 2.5, 3, or 4 times the molar dose required to inhibit FDFT1 activity in the subject. Preferably, the dose is between 0.0001 mg / kg (mass of drug compared to the mass of the patient) and 100 mg / kg, preferably between 0.001 mg / kg and 50 mg / kg, preferably between 0.001 mg / kg and 20 mg / kg, preferably between 0.001 mg / kg and 10 mg / kg, preferably between 0.01 mg / kg and 5 mg / kg, preferably between 0.01 mg / kg and 2 mg / kg, preferably between 0.1 mg / kg and 1.5 mg / kg. g / kg; alternatively, 0.2 mg / kg to 1.2 mg / kg. Additionally, a therapeutically effective amount or prophylactically effective amount may be defined in terms of inhibition of FDFT1 activity, e.g., an amount that means that FDFT1 activity is reduced by at least 10, 20, 30, 40, 50, 60, 70, 80, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% compared to FDFT1 activity in the absence of treatment. Dosage and frequency may be adjusted to maintain FDFT1 activity at a desired level, which may be, for example, 10% or less, e.g., 9, 8, 7, 6, 5, 4, 3, 2, or 1% or less, compared to FDFT1 activity in the absence of treatment. When a dose is given, this refers to the dose of an agent that is a FDFT1 inhibitor or a pharmaceutically acceptable salt thereof.

[0047] FDFT1 activity can be measured by standard assays known in the art, for example, by measuring squalene production as a proxy measure of FDFT1 activity. Suitable methods for measuring squalene synthesis are known in the art, for example, by measuring the radioactive product of liver microsomes incubated with tritiated farnesyl pyrophosphate (FPP) [3, 4, 5].

[0048] The frequency of the dose that needs to be administered depends on the half-life of the agent involved. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof can be administered as a continuous infusion, in a bolus dose, or on a daily basis, twice daily, or every 2, 3, 4, 5, 6, 7, 10, 15, or 20 or more days. In a preferred embodiment, the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof is administered as a bolus dose on a daily basis.

[0049] The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof can be administered for a suitable period determined by a clinician. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof can be administered for up to 30 days, up to 21 days, up to 14 days, or up to 7 days, for example, up to 1, 2, 3, 4, 5, 6, or 7 days. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof can be administered daily for up to 30 days, up to 21 days, up to 14 days, or up to 7 days, for example, up to 1, 2, 3, 4, 5, 6, or 7 days.

[0050] A single dose or multiple doses can be administered. For example, at least 2, 3, 4, 5, 6, 7, or 8 doses can be administered. A single dose is one embodiment. The exact dosage and frequency of administration can also depend on the patient's condition at the time of administration. Factors that can be taken into consideration when determining dosage include the need for treatment or prevention, the severity of the patient's disease state, the patient's general health, age, weight, sex, diet, time and frequency of administration, drug combinations, reaction sensitivities, and the patient's tolerance or response to treatment. The exact amount can be determined by routine experimentation, but ultimately can be left to the discretion of the clinician.

[0051] As used herein, the term "treatment" (also "treat" or "treating") refers to any administration of a therapeutic agent according to a therapeutic regimen that achieves a desired effect in terms of partially or completely alleviating, ameliorating, relieving, inhibiting, delaying the onset of, reducing the severity of, and / or reducing the occurrence of one or more symptoms or characteristics of a particular disease, disorder, and / or condition. In some embodiments, administration of a therapeutic agent according to a therapeutic regimen correlates with achieving a desired effect. Such treatment may be treatment of a subject who does not exhibit signs of the associated disease, disorder, and / or condition and / or a subject who exhibits only early signs of the disease, disorder, and / or condition. Alternatively or additionally, such treatment may be treatment of a subject who exhibits one or more established signs of the associated disease, disorder, and / or condition. In some embodiments, treatment may be treatment of a subject who has been diagnosed with the associated disease, disorder, and / or condition. In some embodiments, treatment may be treatment of a subject who is known to have one or more susceptibility factors that are statistically correlated with an increased risk of developing the associated disease, disorder, and / or condition.

[0052] As used herein, "prevent" refers to delaying or arresting the onset, development, or progression of a disease, disorder, or condition for a period of time ranging from minutes to indefinite. "Prevent" also means reducing the risk of developing a disease, disorder, or condition.

[0053] As used herein, "modulation" refers to a change in the quantity or quality of a molecule, function, or activity compared to the quantity or quality of the molecule, function, or activity prior to modulation. For example, modulation includes changes in either an increase (stimulation or induction) or decrease (inhibition or reduction) of gene expression.

[0054] "Pharmaceutically" or "pharmaceutically acceptable" refers to molecular entities and compositions that do not produce adverse allergic or other unpleasant reactions when administered to mammals, particularly humans, as appropriate. A pharmaceutically acceptable carrier or excipient refers to any type of non-toxic solid, semi-solid, or liquid filler, diluent, encapsulating material, or formulation aid. The form, route of administration, dosage, and regimen of a pharmaceutical composition will naturally depend on the condition being treated, the severity of the disease, the age, weight, and sex of the patient, and the like. In some embodiments, the pharmaceutically acceptable carrier or diluent is sterile saline. In some embodiments, such sterile saline is pharmaceutical-grade saline.

[0055] The term "target cell" refers to a specific cell type of interest in which the functional results of FDFT1 inhibition may be desired. In some embodiments, the target cell is an intestinal cell. In some embodiments, the target cell is an intestinal epithelial cell.

[0056] As used herein, the term "comprising" means including the specified method steps or elements, but that such steps or elements are not inclusive of an exclusive list and therefore that additional steps or elements may be present.

[0057] Furthermore, to the extent the term "includes" is used in either the detailed description or the claims, such term is intended to be inclusive in the same manner as the term "comprising" is interpreted when used as a transitional term in a claim.

[0058] In some embodiments, the FDFT1 inhibitor comprises a small molecule such as lapaquistat described herein. In some embodiments, the FDFT1 inhibitor comprises a small molecule such as YM-53601 described herein. In some embodiments, the FDFT1 inhibitor is an inhibitory nucleic acid molecule (e.g., siRNA). In some embodiments, the FDFT1 inhibitor comprises an antibody or antigen-binding fragment thereof.

[0059] Parasitic diseases The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof of the present invention can be used to treat parasitic infections. In a specific embodiment of the present invention, the present invention relates to the treatment of intestinal parasitic infections. Such parasitic infections include: (a) Infectious diseases caused by single-cell parasites, such as Cryptosporidium parvum, Cryptosporidium hominis, Cryptosporidium canis, Cryptosporidium felis, Cryptosporidium meleagridis, and Cryptosporidium bovis.

[0060] In particular, the present invention relates to the treatment of cryptosporidiosis caused by Cryptosporidium parvum, Cryptosporidium hominis, Cryptosporidium canis, Cryptosporidium felis, Cryptosporidium meleagridis, and Cryptosporidium bovis. In particular, the present invention relates to the treatment of cryptosporidiosis caused by Cryptosporidium parvum.

[0061] Other parasitic infections that can be treated include those caused by other intracellular parasites that are incapable of endogenous cholesterol biosynthesis, specifically parasites that do not express endogenous squalene synthase.

[0062] Viral diseases The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof of the present invention can be used to treat viral infections. In a specific embodiment of the present invention, the present invention relates to the treatment of intestinal viral infections. Such viral infections include: (a) Rotavirus, Norwalk virus, norovirus (Norwalk-like virus), adenovirus, astrovirus, other caliciviruses, and parvoviruses.

[0063] In a specific embodiment of the present invention, the FDFT1 inhibitor of the present invention or a pharmaceutically acceptable salt thereof can be used to treat rotavirus infection.

[0064] Viral gastroenteritis is a very common cause of diarrhea. Foodborne and waterborne outbreaks of viral gastroenteritis are common. The U.S. Centers for Disease Control and Prevention (CDC) estimates that viruses cause 9.2 million cases of food-related illness each year (out of a total of 13.8 million from all causes).

[0065] Several different viruses can cause this disease, including rotavirus, adenovirus, astrovirus, and calicivirus (norovirus and Norwalk virus). The two main causes of human viral gastroenteritis (rotavirus and Norwalk virus) are carried in the intestines of most domestic animals and many wild animals. Fecal-oral spread from animals to humans or from human to human can cause diarrhea. Rotavirus disease (winter diarrhea) is most common among infants and young children, while Norwalk virus disease (summer diarrhea) affects school-age children and adults.

[0066] Rotaviruses belong to the Reoviridae family, i.e., they are naked double-stranded RNA viruses with a double icosahedral capsid.

[0067] Norwalk virus belongs to the Caliciviridae family, i.e., it is a naked, single-stranded RNA-containing virus with a single icosahedral capsid. Norovirus (i.e., Norwalk-like virus or NLV) is a member of the Caliciviridae family and is a well-recognized etiological agent of nonbacterial acute gastroenteritis. The virus is transmitted via the fecal-oral route by contaminated hands, directly from person to person, through contaminated food or water, or by contact with contaminated surfaces or vomit. Adenovirus serotypes 40 and 41 are most commonly associated with infant diarrhea.

[0068] The virus invades and destroys mature epithelial cells of the middle and upper villi, causing a decrease in sodium and water absorption from the intestinal lumen.

[0069] Symptoms include mild fever, abdominal pain, watery diarrhea, nausea, and vomiting. Rotavirus usually causes vomiting and fever in infants under the age of 2. Older people may also have problems with this virus. The incubation period is 2-4 days. Diarrhea may last for a long time and lead to dehydration.

[0070] Adenoviruses cause symptoms similar to rotavirus infection, except that they tend to affect infants older than 1 month. Complications can include intussusception. Norovirus symptoms last 12 to 60 hours and are characterized by sudden onset of low-grade fever, nausea, vomiting, and watery diarrhea. The incubation period is 12 to 48 hours. These viruses can infect both children and adults.

[0071] In one embodiment of the present invention, the FDFT1 inhibitors or pharmaceutically acceptable salts thereof described herein treat or ameliorate one or more symptoms of an enteric viral infection, as described above.

[0072] bacterial disease The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof of the present invention can be used to treat bacterial infections. In a specific embodiment of the present invention, the present invention relates to the treatment of intestinal bacterial infections. Such bacterial infections include: (a) Salmonella, such as diseases caused by Salmonella enterica or Salmonella bongori.

[0073] In certain embodiments of the present invention, the FDFT1 inhibitors of the present invention or pharmaceutically acceptable salts thereof can be used to treat bacterial infections. In certain embodiments of the present invention, the FDFT1 inhibitors of the present invention or pharmaceutically acceptable salts thereof can be used to treat Salmonella infections.

[0074] Salmonella species are typically intracellular pathogens that can invade different cell types, including epithelial cells, M cells, macrophages, and dendritic cells.

[0075] Symptoms of Salmonella include back pain or spondylosis. It can manifest as five clinical patterns: gastrointestinal infection, enteric fever, bacteremia, localized infection, and chronic colonization. Initial symptoms include nonspecific fever, weakness, and muscle pain, among others. In the bacteremic state, the infection can spread to any part of the body, causing localized infection or forming abscesses. Some forms of localized Salmonella infection include arthritis, urinary tract infection, central nervous system infection, bone infection, and soft tissue infection. The infection can remain latent for long periods and become activated when reticuloendothelial cell function declines, resulting in secondary disseminated infection within the bones months or years after acute salmonellosis.

[0076] In one embodiment of the present invention, the FDFT1 inhibitors or pharmaceutically acceptable salts thereof described herein treat or ameliorate one or more symptoms of an enterobacterial infection, as described above. In one embodiment of the present invention, the FDFT1 inhibitors or pharmaceutically acceptable salts thereof described herein treat or ameliorate one or more symptoms of a Salmonella infection, as described above.

[0077] Cryptosporidiosis Common signs and symptoms of intestinal cryptosporidiosis include: Moderate to severe watery diarrhea that may contain mucus and rarely contains blood or white blood cells (in very severe cases, diarrhea may be profuse and be accompanied by cholera-like malabsorption and hypovolemia) ·Slight fever ·Spasmodic abdominal pain ·dehydration ·Weight loss Fatigue Nausea and vomiting -Tenderness in the upper or right upper quadrant of the abdomen

[0078] Other symptoms include: Reactive arthritis (which can affect the hands, knees, ankles, and feet) ·jaundice Ascites

[0079] Symptoms of upper respiratory tract cryptosporidiosis include: Inflammation of the nasal mucosa, sinuses, larynx, or trachea ·Rhinorrhea Changes in voice (e.g., hoarseness)

[0080] Symptoms of lower respiratory tract cryptosporidiosis include: ·cough ·shortness of breath Fever Hypoxemia may occur

[0081] In one embodiment of the present invention, the FDFT1 inhibitors or pharmaceutically acceptable salts thereof described herein treat or ameliorate one or more symptoms of cryptosporidiosis infection as described above.

[0082] Pharmaceutical Compositions of Drugs As used herein, "pharmaceutical composition" refers to a mixture of substances suitable for administration to an individual. A pharmaceutical composition may contain one or more pharmaceutically active ingredients combined with one or more pharmaceutically acceptable excipients or diluents. For example, a pharmaceutical composition may contain one or more active agents and a sterile aqueous solution.

[0083] As used herein, "pharmaceutically acceptable salt" refers to a physiologically and pharmaceutically acceptable salt of a FDFT1 inhibitor, i.e., a salt that retains the desired biological activity of the FDFT1 inhibitor and does not impart undesirable toxicological effects thereto. Such salts include acetate, aspartate, benzoate, besylate, bromide / hydrobromide, bicarbonate / carbonate, bisulfate / sulfate, camphorsulfonate, chloride / hydrochloride, chlortheophyllonate, citrate, ethanedisulfonate, fumarate, gluceptate, gluconate, glucuronate, oleate, oxalate, palmitate, pamoate, phosphate / hydrogenphosphate / dihydrogenphosphate / dihydrogenphosphate, propionate, stearate, succinate, sulfosalicylate, tartrate, tosylate, trifluoroacetate, and the like. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc. In one embodiment, the salt is an acetate salt.

[0084] The compounds of the present invention may include their isomers, salts, and solvates. Certain compounds of the present invention may exist in one or more particular geometric, tautomeric, conformational, or anomeric forms, including, but not limited to, cis and trans forms, E and Z forms, C, t and r forms, endo and exo forms, keto, enol, and enolate forms, syn and anti forms, synclinal and anticlinal forms, [alpha] and [beta] forms, axial and equatorial forms, boat, chair, twist, envelope, and half-chair forms, and combinations thereof, hereinafter collectively referred to as "isomers" (or "isomeric forms").

[0085] The pharmaceutical compositions prepared according to the present invention can be prepared and administered in a variety of dosage forms. For example, these pharmaceutical compositions can be prepared in an inert pharmaceutically acceptable carrier, either solid or liquid. Solid form preparations include powders, tablets, dispersible granules, capsules, cachets, and suppositories. Other solid and liquid form preparations can be prepared according to methods known in the art and administered orally in appropriate formulations or parenterally, such as intravenous, intramuscular, or subcutaneous injection as liquid formulations.

[0086] The term "solvate" refers to a molecular complex of a compound containing one or more solvent molecules. Such solvent molecules are commonly used in the pharmaceutical arts and are known to be innocuous with respect to the compound, e.g., water, ethanol, etc.

[0087] Another aspect of the present invention also relates to a pharmaceutical product or diagnostic aid comprising a composition according to the present invention or a FDFT1 inhibitor according to the present invention and, where appropriate, suitable excipients and additives such as physiological saline solution, stabilizers, or protease inhibitors.

[0088] Suitable pharmaceutically acceptable excipients, such as fats, water, physiological saline, alcohol (e.g., ethanol), glycerol, polyols, aqueous glucose solutions, fillers, disintegrants, binders, lubricants, wetting agents, stabilizers, emulsifiers, dispersants, preservatives, sweeteners, colorants, flavorings or fragrances, thickeners, diluents, buffer substances, solvents or solubilizers, chemicals for achieving a storage effect, salts for modifying osmotic pressure, coating agents or antioxidants, polysaccharides such as lactose or glucose; corn, wheat, or rice starch; fatty acids such as stearic acid; inorganic salts such as magnesium aluminometasilicate or anhydrous calcium phosphate; synthetic polymers such as polyvinylpyrrolidone or polyalkylene glycols; alcohols such as stearyl alcohol or benzyl alcohol; synthetic cellulose derivatives such as methylcellulose, carboxymethylcellulose, ethylcellulose, or hydroxypropylmethylcellulose; and other conventionally used additives such as gelatin, talc, vegetable oils, and gum arabic.

[0089] The pharmaceutical compositions may also contain preservatives, solubilizers, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, odorants, buffers, coating agents, and / or antioxidants.

[0090] Combination therapy In some embodiments, the invention features compositions (e.g., one or more compositions, formulations, or dosage forms) or pharmaceutical combinations including a FDFT1 inhibitor according to the invention and one or more additional therapeutic agents. In some embodiments, the invention features compositions (e.g., one or more compositions, formulations, or dosage forms) or pharmaceutical combinations including a therapeutic agent according to the invention and one or more additional therapeutic agents.

[0091] In some embodiments, the one or more additional therapeutic agents comprise compounds (i.e., drugs) that inhibit cholesterol biosynthesis and / or reduce the amount of cholesterol in the subject's blood. For example, the one or more additional therapeutic agents can include a statin, such as lovastatin or atorvastatin.

[0092] In some embodiments, the FDFT1 inhibitor is lapaquistat and is administered in combination with a statin, preferably lovastatin or atorvastatin.

[0093] In some embodiments, the composition includes a pharmaceutically acceptable carrier or diluent. In some embodiments, the FDFT1 inhibitor and one or more additional therapeutic agents can be present in a single composition or as two or more different compositions. The FDFT1 inhibitor and one or more additional therapeutic agents can be administered via the same administration route or via different administration routes. The FDFT1 inhibitor and one or more additional therapeutic agents can be administered simultaneously or sequentially. In some embodiments, a pharmaceutical combination includes the FDFT1 inhibitor and one or more additional therapeutic agents, either separately or together.

[0094] As used herein, the terms "combination treatment," "combination therapy," or "combination therapy" refer to treatment using two or more pharmaceutical agents. Combination therapy can be dual therapy or bitherapy.

[0095] As used herein, the term "concurrent administration" refers to the administration of two active ingredients by the same route at the same time or substantially the same time. The term "separate administration" refers to the administration of two active ingredients by different routes at the same time or substantially the same time. The term "sequential administration" refers to the administration of two active ingredients at different times, and the routes of administration may be the same or different.

[0096] kit The compounds and compositions of the present invention can be packaged in a kit, optionally with one or more other pharmaceutical agents. Non-limiting examples of kits include those containing, for example, two or more pills, a pill and a powder, a suppository and a liquid in a vial, or two topical creams. The kit can include optional components to aid in administering a unit dose to a subject, such as a vial for reconstituting a powder form, a syringe for injection, a customized IV delivery system, or an inhaler. Additionally, a unit dose kit can contain instructions for preparing and administering the composition. The kit can be manufactured as a single-use unit dose for one subject, multiple uses for a specific subject (at a fixed dose, or where individual compounds may have varying potencies as treatment progresses), or the kit can contain multiple doses suitable for administration to multiple subjects ("bulk packaging"). Kit components can be assembled in cartons, blister packs, bottles, and tubes. The kit components can be placed separately from each other, for example, in separate containers. The kit can include instructions for use.

[0097] Route of administration The FDFT1 inhibitor or pharmaceutical composition may be administered by different routes, including orally, parenterally, sublingually, intradermally, transdermally, rectally, transmucosally, topically, via inhalation, via buccal administration, intrapleurally, intravenously, intraarterially, intraperitoneally, subcutaneously, intramuscularly, intranasally, intrathecally, and / or intraarticularly, or a combination thereof. In some embodiments, the agent or pharmaceutical composition is administered orally. In some embodiments, the agent or pharmaceutical composition is administered intravenously.

[0098] The present invention is further illustrated in the following examples. It should be understood that these examples, while showing embodiments of the present invention, are provided by way of illustration only. From the above discussion and these examples, those skilled in the art can ascertain the essential features of the present invention and can make various changes and modifications to the present invention to adapt it to various uses and conditions without departing from the spirit and scope thereof. Thus, various modifications of the present invention, in addition to those shown and described herein, will be apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims.

[0099] Example: Non-limiting combinations The present invention also extends to at least the following:

[0100] FDFT1 inhibitors and statins In the present invention, FDFT1 inhibitors may be used in combination with drugs that inhibit cholesterol biosynthesis and / or reduce the amount of cholesterol in the subject's blood (e.g., statins).

[0101] The present invention provides FDFT1 inhibitors for use in treating infections caused by intracellular pathogens that do not express endogenous squalene synthase. The FDFT1 inhibitors may be combined with statins for simultaneous, separate, or sequential administration. The invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0102] The present invention provides lapaquistat or YM53601 for use in treating infections caused by intracellular pathogens that do not express endogenous squalene synthase. Lapaquistat or YM53601 may be combined with a statin for simultaneous, separate, or sequential administration. The present invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0103] The present invention provides lapaquistat or YM53601 for use in treating parasitic infections caused by intracellular parasites that do not express endogenous squalene synthase. Lapaquistat or YM53601 may be combined with a statin for simultaneous, separate, or sequential administration. The present invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0104] The present invention provides lapaquistat or YM53601 for use in treating Cryptosporidium infections. Lapaquistat or YM53601 may be combined with a statin for simultaneous, separate, or sequential administration. The present invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0105] The present invention provides lapaquistat or YM53601 for use in the treatment of rotavirus infection. Lapaquistat or YM53601 may be combined with a statin for simultaneous, separate, or sequential administration. The present invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0106] The present invention provides lapaquistat or YM53601 for use in treating Salmonella infections. Lapaquistat or YM53601 may be combined with a statin for simultaneous, separate, or sequential administration. The present invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0107] The present invention provides lapaquistat for use in treating infections by intracellular pathogens that do not express endogenous squalene synthase. Lapaquistat may be combined with a statin for simultaneous, separate, or sequential administration. The invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0108] The present invention provides lapaquistat for use in the treatment of intracellular parasitic infections by parasites that do not express endogenous squalene synthase. Lapaquistat may be combined with a statin for simultaneous, separate, or sequential administration. The invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0109] The present invention provides lapaquistat for use in the treatment of Cryptosporidium infections. Lapaquistat may be combined with a statin for simultaneous, separate, or sequential administration. The invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0110] The present invention provides lapaquistat for use in the treatment of rotavirus infection. Lapaquistat may be combined with a statin for simultaneous, separate, or sequential administration. The invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0111] The present invention provides lapaquistat for use in treating Salmonella infections. Lapaquistat may be combined with a statin for simultaneous, separate, or sequential administration. The invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0112] The present invention provides YM53601 for use in treating infections caused by intracellular pathogens that do not express endogenous squalene synthase. YM53601 may be combined with a statin for simultaneous, separate, or sequential administration. The present invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0113] The present invention provides YM53601 for use in treating parasitic infections caused by intracellular parasites that do not express endogenous squalene synthase. YM53601 may be combined with a statin for simultaneous, separate, or sequential administration. The present invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0114] The present invention provides YM53601 for use in the treatment of Cryptosporidium infections. YM53601 may be combined with a statin for simultaneous, separate, or sequential administration. The present invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0115] The present invention provides YM53601 for use in the treatment of rotavirus infection. YM53601 may be combined with a statin for simultaneous, separate, or sequential administration. The present invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0116] The present invention provides YM53601 for use in treating Salmonella infections. YM53601 may be combined with a statin for simultaneous, separate, or sequential administration. The present invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0117] The present invention provides a. FDFT1 inhibitor; b. with statins The present invention provides a combination for use in treating infections caused by intracellular pathogens that do not express endogenous squalene synthase. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0118] The present invention provides a. Lapaquistat or YM53601, b. with statins The present invention provides a combination for use in treating infections caused by intracellular pathogens that do not express endogenous squalene synthase. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0119] The present invention provides a. Lapaquistat or YM53601, b. with statins The present invention provides a combination for use in the treatment of intracellular parasitic infections caused by parasites that do not express endogenous squalene synthase. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0120] The present invention provides a. Lapaquistat or YM53601, b. with statins The present invention provides a combination for use in the treatment of Cryptosporidium infections. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0121] The present invention provides a. Lapaquistat or YM53601, b. with statins The present invention provides a combination for use in the treatment of rotavirus infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0122] The present invention provides a. Lapaquistat or YM53601, b. with statins The present invention provides a combination for use in the treatment of Salmonella infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0123] The present invention provides a. Lapaquistat, b. with statins The present invention provides a combination for use in the treatment of Cryptosporidium infections. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0124] The present invention provides a. Lapaquistat, b. with statins The present invention provides a combination for use in the treatment of rotavirus infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0125] The present invention provides a. Lapaquistat, b. with statins The present invention provides a combination for use in the treatment of Salmonella infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0126] The present invention provides a.YM53601 and b. with statins The present invention provides a combination for use in the treatment of Cryptosporidium infections. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0127] The present invention provides a.YM53601 and b. with statins The present invention provides a combination for use in the treatment of rotavirus infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0128] The present invention provides a.YM53601 and b. with statins The present invention provides a combination for use in the treatment of Salmonella infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0129] The present invention provides a. Lapaquistat or YM53601, b. With lovastatin The present invention provides a combination for use in treating infections caused by intracellular pathogens that do not express endogenous squalene synthase. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0130] The present invention provides a. Lapaquistat or YM53601, b. With lovastatin The present invention provides a combination for use in the treatment of intracellular parasitic infections caused by parasites that do not express endogenous squalene synthase. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0131] The present invention provides a. Lapaquistat or YM53601, b. With lovastatin The present invention provides a combination for use in the treatment of Cryptosporidium infections. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0132] The present invention provides a. Lapaquistat or YM53601, b. With lovastatin The present invention provides a combination for use in the treatment of rotavirus infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0133] The present invention provides a. Lapaquistat or YM53601, b. With lovastatin The present invention provides a combination for use in the treatment of Salmonella infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0134] The present invention provides a. Lapaquistat, b. With lovastatin The present invention provides a combination for use in the treatment of Cryptosporidium infections. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0135] The present invention provides a. Lapaquistat, b. With lovastatin The present invention provides a combination for use in the treatment of rotavirus infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0136] The present invention provides a. Lapaquistat, b. With lovastatin The present invention provides a combination for use in the treatment of Salmonella infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0137] The present invention provides a.YM53601 and b. With lovastatin The present invention provides a combination for use in the treatment of Cryptosporidium infections. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0138] The present invention provides a.YM53601 and b. With lovastatin The present invention provides a combination for use in the treatment of rotavirus infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0139] The present invention provides a.YM53601 and b. With lovastatin The present invention provides a combination for use in the treatment of Salmonella infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0140] The present invention provides a. Lapaquistat or YM53601, b. With atorvastatin The present invention provides a combination for use in treating infections caused by intracellular pathogens that do not express endogenous squalene synthase. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0141] The present invention provides a. Lapaquistat or YM53601, b. With atorvastatin The present invention provides a combination for use in the treatment of parasitic infections caused by intracellular parasites that do not express endogenous squalene synthase. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0142] The present invention provides a. Lapaquistat or YM53601, b. With atorvastatin The present invention provides a combination for use in the treatment of Cryptosporidium infections. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0143] The present invention provides a. Lapaquistat or YM53601, b. With atorvastatin The present invention provides a combination for use in the treatment of rotavirus infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0144] The present invention provides a. Lapaquistat or YM53601, b. With atorvastatin The present invention provides a combination for use in the treatment of Salmonella infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0145] The present invention provides a. Lapaquistat, b. With atorvastatin The present invention provides a combination for use in the treatment of Cryptosporidium infections. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0146] The present invention provides a. Lapaquistat, b. With atorvastatin The present invention provides a combination for use in the treatment of rotavirus infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0147] The present invention provides a. Lapaquistat, b. With atorvastatin The present invention provides a combination for use in the treatment of Salmonella infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0148] The present invention provides a.YM53601 and b. With atorvastatin The present invention provides a combination for use in the treatment of Cryptosporidium infections. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0149] The present invention provides a.YM53601 and b. With atorvastatin The present invention provides a combination for use in the treatment of rotavirus infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0150] The present invention provides a.YM53601 and b. With atorvastatin The present invention provides a combination for use in the treatment of Salmonella infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0151] FDFT1 inhibitors and other antiparasitic agents The present invention provides FDFT1 inhibitors for use in treating infections caused by intracellular pathogens that do not express endogenous squalene synthase. The FDFT1 inhibitors may be combined with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide) for simultaneous, separate, or sequential administration. The present invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0152] The present invention provides lapaquistat or YM53601 for use in treating infections caused by intracellular pathogens that do not express endogenous squalene synthase. Lapaquistat or YM53601 may be combined with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide) for simultaneous, separate, or sequential administration. The present invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0153] The present invention provides lapaquistat or YM53601 for use in treating parasitic infections caused by intracellular parasites that do not express endogenous squalene synthase. Lapaquistat or YM53601 may be combined with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide) for simultaneous, separate, or sequential administration. The present invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0154] The present invention provides lapaquistat or YM53601 for use in treating Cryptosporidium infections. Lapaquistat or YM53601 may be combined with a statin for simultaneous, separate, or sequential administration. The present invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0155] The present invention provides lapaquistat for use in treating infections caused by intracellular pathogens that do not express endogenous squalene synthase. Lapaquistat may be combined with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide) for simultaneous, separate, or sequential administration. The invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0156] The present invention provides lapaquistat for use in treating intracellular parasitic infections by parasites that do not express endogenous squalene synthase. Lapaquistat may be combined with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide) for simultaneous, separate, or sequential administration. The invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0157] The present invention provides lapaquistat for use in the treatment of Cryptosporidium infections. Lapaquistat may be combined with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide) for simultaneous, separate, or sequential administration. The invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0158] The present invention provides YM53601 for use in treating infections caused by intracellular pathogens that do not express endogenous squalene synthase. YM53601 may be combined with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide) for simultaneous, separate, or sequential administration. The present invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0159] The present invention provides YM53601 for use in treating parasitic infections caused by intracellular parasites that do not express endogenous squalene synthase. YM53601 may be combined with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide) for simultaneous, separate, or sequential administration. The present invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0160] The present invention provides YM53601 for use in the treatment of Cryptosporidium infections. YM53601 may be combined with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide) for simultaneous, separate, or sequential administration. The present invention extends to corresponding methods of treatment, pharmaceutical compositions, combinations, and kits.

[0161] The present invention provides a. FDFT1 inhibitor; b. with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide); The present invention provides a combination for use in treating infections caused by intracellular pathogens that do not express endogenous squalene synthase. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0162] The present invention provides a. Lapaquistat or YM53601, b. with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide); The present invention provides a combination for use in treating infections caused by intracellular pathogens that do not express endogenous squalene synthase. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0163] The present invention provides a. Lapaquistat or YM53601, b. with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide); The present invention provides a combination for use in the treatment of intracellular parasitic infections caused by parasites that do not express endogenous squalene synthase. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0164] The present invention provides a. Lapaquistat or YM53601, b. with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide); The present invention provides a combination for use in the treatment of Cryptosporidium infections. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0165] The present invention provides a. Lapaquistat or YM53601, b. with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide); The present invention provides a combination for use in the treatment of rotavirus infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0166] The present invention provides a. Lapaquistat or YM53601, b. with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide); The present invention provides a combination for use in the treatment of Salmonella infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0167] The present invention provides a. Lapaquistat, b. with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide); The present invention provides a combination for use in the treatment of Cryptosporidium infections. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0168] The present invention provides a. Lapaquistat, b. with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide); The present invention provides a combination for use in the treatment of rotavirus infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0169] The present invention provides a. Lapaquistat, b. with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide); The present invention provides a combination for use in the treatment of Salmonella infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0170] The present invention provides a.YM53601 and b. with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide); The present invention provides a combination for use in the treatment of Cryptosporidium infections. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0171] The present invention provides a.YM53601 and b. with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide); The present invention provides a combination for use in the treatment of rotavirus infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0172] The present invention provides a.YM53601 and b. with nitazoxanide, paromomycin, or halofuginone (e.g., nitazoxanide); The present invention provides a combination for use in the treatment of Salmonella infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0173] The present invention provides a. Lapaquistat or YM53601, b. With nitazoxanide The present invention provides a combination for use in the treatment of Cryptosporidium infections. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0174] The present invention provides a. Lapaquistat or YM53601, b. With nitazoxanide The present invention provides a combination for use in the treatment of rotavirus infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0175] The present invention provides a. Lapaquistat or YM53601, b. With nitazoxanide The present invention provides a combination for use in the treatment of Salmonella infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0176] The present invention provides a. Lapaquistat, b. With nitazoxanide The present invention provides a combination for use in the treatment of Cryptosporidium infections. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0177] The present invention provides a. Lapaquistat, b. With nitazoxanide The present invention provides a combination for use in the treatment of rotavirus infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0178] The present invention provides a. Lapaquistat, b. With nitazoxanide The present invention provides a combination for use in the treatment of Salmonella infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0179] The present invention provides a.YM53601 and b. With nitazoxanide The present invention provides a combination for use in the treatment of Cryptosporidium infections. The components of the combination may be for separate, simultaneous, or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions, and kits.

[0180] The present invention provides a.YM53601 and b. With nitazoxanide The present invention provides a combination for use in the treatment of rotavirus infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0181] The present invention provides a.YM53601 and b. With nitazoxanide The present invention provides a combination for use in the treatment of Salmonella infection. The components of the combination may be for separate, simultaneous or sequential administration. The invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits. Triple Combination

[0182] The present invention provides a. FDFT1 inhibitor; b. Statins, c. With one or more other drugs used in the treatment or prevention of parasitic infections; The present invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0183] The present invention provides a. FDFT1 inhibitor; b. Statins, c. with nitazoxanide, paromomycin, or halofuginone; The present invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0184] The present invention provides a. Lapaquistat or YM53601, b. Statins, c. with nitazoxanide, paromomycin, or halofuginone; The present invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0185] The present invention provides a. Lapaquistat or YM53601, b. Statins, c. With nitazoxanide The present invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0186] The present invention provides a. Lapaquistat, b. Statins, c. With nitazoxanide The present invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0187] The present invention provides a.YM53601 and b. Statins, c. With nitazoxanide The present invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0188] The present invention provides a. Lapaquistat or YM53601, B. lovastatin, c. with nitazoxanide, paromomycin, or halofuginone; The present invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0189] The present invention provides a. Lapaquistat or YM53601, B. lovastatin, c. With nitazoxanide The present invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0190] The present invention provides a. Lapaquistat, B. lovastatin, c. With nitazoxanide The present invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0191] The present invention provides a.YM53601 and B. lovastatin, c. With nitazoxanide The present invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0192] The present invention provides a. Lapaquistat or YM53601, b. Atorvastatin, c. with nitazoxanide, paromomycin, or halofuginone; The present invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0193] The present invention provides a. Lapaquistat or YM53601, b. Atorvastatin, c. With nitazoxanide The present invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0194] The present invention provides a. Lapaquistat, b. Atorvastatin, c. With nitazoxanide The present invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits.

[0195] The present invention provides a.YM53601 and b. Atorvastatin, c. With nitazoxanide The present invention extends to corresponding uses, methods of treatment, pharmaceutical compositions and kits. [Example]

[0196] Example 1 - Microscopy-based genome-wide CRISPR-Cas9 screen for host genes affecting Cryptosporidium growth in vitro HCT-8 cells (ATCC; CCL-244) were transformed using the Genome-CRISP-Inducible Cas9 Human AAVS1 Safe Harbor Knock-in Kit (Catalog No. SH016) to generate a cell line capable of doxycycline-inducible Cas9 expression. A single clone exhibiting the most efficient gene knockdown upon CRISPR guide RNA transfection with doxycycline treatment was selected. 200 nM of crRNA guide from a complete human genome library (Dharmacon Human Edit-R-Genome; Catalog No. GP / GC-005005-xx) was mixed with tracrRNA at a 1:1 ratio and transferred to a 384-well plate. Each well contained four crRNA guides targeting a single gene. Each plate also contained non-targeting crRNA guides, as well as positive controls corresponding to gene targets previously identified to reduce and increase Cryptosporidium growth. The plates were sealed and frozen at -20°C until use.

[0197] Plates were thawed at room temperature, and transfectant (Dharmafect2; catalog number T-2002-03, dissolved in Opti-MEM) was dispensed into each well. Cas9-HCT-8 cells were then seeded into all wells (2250 cells / well) in doxycycline-containing medium (RPMI with 10% FCS). Plates were incubated at 37°C and 5% CO for 72 hours. Cryptosporidium parvum oocysts (Bunchgrass Farms; Dreary, Idaho, USA) were prepared for infection by bleach treatment (1% sodium hypochlorite) on ice for 5 minutes to remove bacterial contaminants, followed by a washing step and incubation in 0.75% sodium taurocholate for 10 minutes at 37°C to induce excystation. Follicles were resuspended in infection medium (RPMI with 1% FCS) containing doxycycline and distributed to all wells (12,500 follicles / well). Plates were incubated at 37°C, 5% CO for 49 hours.

[0198] Plates were fixed by adding concentrated paraformaldehyde (PFA) to each well to produce a final concentration of 4% PFA. After 20 minutes of fixation, plates were washed three times, followed by 10 minutes of permeabilization (0.25% Triton X-100 in PBS) and 1 hour of blocking (4% BSA in PBS). Cells were stained overnight with a Cryptosporidium female-specific antibody (rat anti-COWP1) in 1% BSA. The next day, plates were washed with PBS and incubated with a fluorescently conjugated lectin (VVL-Fluorescein, VectorLabs; catalog number FL-1231-2) to detect total Cryptosporidium parasites, an anti-rat antibody conjugated to AlexaFluor-647, AlexaFluor-546 conjugated to phalloidin to detect host cell actin, and Hoechst to detect host cells. Plates were incubated for 90 minutes, washed with PBS, and sealed.

[0199] All plates were imaged using the Opera Phenix high-content screening system (PerkinElmer) to image host cells, host actin, parasites, and any females among those parasites. Five fields were photographed per well. All images were analyzed using Harmony high-content imaging and analysis software (PerkinElmer), outputting information in the form of host and parasite numbers, number of females, recruitment of host actin to parasites, and size information for each parasite. The resulting information was subjected to a normalization algorithm to account for any plate edge effects across all 183 384-well plates used in the experiment.

[0200] Example 2 - In vitro IC50 curve with Lapaquistat HCT cells (ATCC; CCL-244) were seeded in 96-well plates at a density of 30,000 cells / well in complete medium (RPMI containing 10% FCS) and grown for 48 hours. Cryptosporidium parvum oocysts (Bunchgrass Farms; Dreary, Idaho, USA) were prepared for infection by bleaching (1% sodium hypochlorite) for 5 minutes on ice to remove bacterial contaminants, followed by a washing step, and then incubating in 0.75% sodium taurocholate for 10 minutes at 37°C to induce excystation. Oocytes were resuspended in infection medium (RPMI containing 1% FCS) and added to the cells in 100 μL of medium (20,000 oocysts / well).

[0201] A 10 mM solution of lapaquistat acetate (MedChem Express; catalog number HY-16274-1mg) was made using DMSO as the solvent. From this stock, half-log (3.16-fold) serial dilutions were made in infection medium at twice the intended final concentration. Three hours post-infection, 100 μL of each drug dilution was added to the wells. Each drug concentration consisted of six technical replicates. Plates were incubated at 37°C, 5% CO2 for a total of 49 hours post-infection.

[0202] Cells were fixed in 4% paraformaldehyde for 20 minutes and then washed three times with PBS. Cells were permeabilized (0.25% Triton X-100 in PBS) for 10 minutes and blocked (4% BSA in PBS) for 1 hour. They were then incubated overnight in 1% BSA with a Cryptosporidium female-specific antibody (rat anti-COWP1). The next day, the plates were washed with PBS and incubated with a fluorescently conjugated lectin (VVL-Fluorescein, VectorLabs; catalog number FL-1231-2) to detect all Cryptosporidium parasites, an anti-rat antibody conjugated to AlexaFLuor-647, and Hoechst to detect host cells. The plates were stained for 90 minutes and washed with PBS. The plates were then photographed using a Cytation multimode cell imaging reader (BioTek) to count host nuclei, total parasite numbers, and the number of female parasites among them.

[0203] Example 3 - Results of Lapaquistat Treatment of Cryptosporidium-Infected Cells Cryptosporidium parasites are obligate intracellular parasites that depend on host cells for survival. To identify host genes required for Cryptosporidium growth and development, we developed a high-throughput microscopy-based CRISPR assay to measure parasite number, size, and development in human intestinal epithelial cells (HCT-8 adenocarcinoma) (Figure 1A). In vitro, Cryptosporidium replicates intracellularly and develops into male and female sexual stages. Using antibodies specific for female parasites, we were able to detect and quantitate this development.

[0204] Through this screen, we found that the cholesterol biosynthesis pathway, specifically FDFT1, a gene responsible for squalene synthesis, is required for Cryptosporidium parasite growth and development (Figure 1B). FDFT1 is the rate-limiting step in the cholesterol biosynthesis pathway, and TAK-475, or lapaquistat, is a highly specific inhibitor of FDFT1 originally developed to treat hypercholesterolemia [6, 7, 8]. Treatment of Cryptosporidium-infected intestinal cell monolayers showed that lapaquistat was effective in blocking both parasite growth (IC50 7.7 μM) and development (IC50 5.2 μM) in vitro (Figure 1C).

[0205] Lapaquistat was originally developed by Takeda Pharmaceuticals for the treatment of hypercholesterolemia, but was ultimately abandoned after Phase 3 clinical trials when it was discovered that patients in the high-dose group exhibited elevated liver enzymes after 8 weeks of treatment. Because lapaquistat has demonstrated efficacy against Cryptosporidium and the drug already has substantial safety data (over three large-scale clinical trials), we believe there is great potential for repurposing lapaquistat to treat Cryptosporidium. Cryptosporidium treatment does not require chronic administration, and lapaquistat's low bioavailability could allow the drug to concentrate at the site of intestinal infection, increasing its efficacy and allowing the use of lower doses [7, 8]. Furthermore, because many intracellular pathogens (including viruses and bacteria) require cholesterol biosynthesis within infected host cells, we believe that inhibition of FDFT1 could be used for broad-spectrum treatment of intestinal infections.

[0206] Example 4 - Results of YM-53601 treatment of Cryptosporidium-infected cells HCT cells (ATCC; CCL-244) were seeded in 96-well plates at a density of 30,000 cells / well in complete medium (RPMI with 10% FCS) and grown for 48 hours.

[0207] Cryptosporidium parvum oocysts (Bunchgrass Farms; Dreary, Idaho, USA) were prepared for infection by bleaching (1% sodium hypochlorite) for 5 min on ice to remove bacterial contaminants, followed by a washing step and incubation in 0.75% sodium taurocholate for 10 min at 37°C to induce excystation. Follicles were resuspended in infection medium (RPMI with 1% FCS) and added to the cells in 100 μL of medium (20,000 follicles / well).

[0208] A 10 mM solution of YM-53601 (AdooQ Bioscience, reference A13483) was made using DMSO as the solvent. From this stock, half-log (3.16-fold) serial dilutions were made in infection medium at twice the intended final concentration. Three hours post-infection, 100 μL of each drug dilution was added to the wells. Each drug concentration consisted of six technical replicates. Plates were incubated at 37°C, 5% CO2 for a total of 49 hours post-infection.

[0209] Cells were fixed in 4% paraformaldehyde for 20 minutes and then washed three times with PBS. Cells were permeabilized (0.25% Triton X-100 in PBS) for 10 minutes and blocked (4% BSA in PBS) for 1 hour. Cells were then incubated with a Cryptosporidium female-specific antibody (rat anti-COWP1) in 1% BSA overnight. The next day, plates were washed with PBS and incubated with a fluorescently conjugated lectin (VVL-Fluorescein, VectorLabs; catalog number FL-1231-2) to detect all Cryptosporidium parasites, an anti-rat antibody conjugated to AlexaFluor-647, and Hoechst to detect host cells. Plates were stained for 90 minutes and washed with PBS.

[0210] The plates were then photographed using a Cytation cytophotography multimode reader (BioTek) to count host nuclei, total number of parasites, and number of female parasites among them.

[0211] Example 5 - Lapaquistat synergistically combined with statins Intestinal epithelial cells (HCT-8) were infected with Cryptosporidium parasites and treated with increasing concentrations of lapaquistat acetate or lovastatin, either alone or in combination. 48 hours after infection, cells were fixed and stained with a lectin that specifically marks parasites and Hoechst dye that specifically labels DNA. Cells and parasites were then visualized under an Opera Phoenix microscope, and infection rates were calculated as the number of parasites divided by the number of host cells. We found that the potency of lapaquistat in restricting Cryptosporidium growth was synergistically increased when combined with lovastatin (as defined in Meyer et al., PMID 30797775) (Figure 3). In this regard, the IC50 values ​​for lapaquistat alone, lovastatin alone, and the combination were 1.2 μM, 4.1 μM, and 0.32 μM, respectively. Thus, lapaquistat acts in a synergistic manner in combination with statins against Cryptosporidium infections.

[0212] Equivalents and Scope Those skilled in the art will appreciate that the present invention is defined by the appended claims, rather than by the specific embodiment examples or other descriptions contained herein.

[0213] Similarly, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0214] Unless otherwise defined above, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present disclosure. Generally, the nomenclature used in connection with, and techniques of, cell and tissue culture, molecular biology, immunology, genetics, and protein and nucleic acid chemistry described herein are well known and commonly used in the art or according to manufacturer's specifications.

[0215] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention. To the extent section headings are used, they should not be construed as necessarily limiting.

[0216] Embodiment The present invention also provides the embodiments described below. 1. A method for treating or preventing an infectious disease, comprising administering to a patient in need thereof a therapeutically or prophylactically effective amount of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof. 2. The method of embodiment 1, wherein the infection is an infection by a pathogen incapable of endogenous cholesterol biosynthesis. 3. The method of embodiment 1 or 2, wherein the infectious disease is an infection caused by a pathogen incapable of endogenous squalene synthesis. 4. The method of any preceding embodiment, wherein the infection is an infection by a pathogen that does not express endogenous squalene synthase. 5. The method of any preceding embodiment, wherein the infection is a parasitic, viral, or bacterial infection. 6. The method of any preceding embodiment, wherein the infection is a Cryptosporidium infection. 7. The method of any one of embodiments 1-5, wherein the infection is a rotavirus infection. 8. The method of any one of embodiments 1-5, wherein the infection is a Salmonella infection. 9. A method for treating or preventing a parasitic infection, comprising administering to a patient in need thereof a therapeutically or prophylactically effective amount of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof. 10. A method for treating or preventing a Cryptosporidium infection, comprising administering to a patient in need thereof a therapeutically or prophylactically effective amount of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof. 11. A method for treating or preventing a viral infection, comprising administering to a patient in need thereof a therapeutically or prophylactically effective amount of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof. 12. A method for treating or preventing a rotavirus infection, comprising administering to a patient in need thereof a therapeutically or prophylactically effective amount of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof. 13. A method for treating or preventing a bacterial infection, comprising administering to a patient in need thereof a therapeutically or prophylactically effective amount of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof. 14. A method for treating or preventing a Salmonella infection, comprising administering to a patient in need thereof a therapeutically or prophylactically effective amount of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof. 15. A farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof for use in a method for treating or preventing an infectious disease. 16. A farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof for use according to embodiment 15, wherein the infectious disease is an infection caused by a pathogen incapable of endogenous cholesterol biosynthesis. 17. A farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof for use according to embodiment 15 or 16, wherein the infection is an infection caused by a pathogen incapable of endogenous squalene synthesis. 18. The farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 17, wherein the infectious disease is an infection caused by a pathogen that does not express endogenous squalene synthase. 19. The farnesyl-diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 18, wherein the infection is a parasitic, viral, or bacterial infection. 20. A farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof for use according to embodiment 19, wherein the infection is a Cryptosporidium infection. 21. The farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof for use according to embodiment 19, wherein the infection is a rotavirus infection. 22. The farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof for use according to embodiment 19, wherein the infection is a Salmonella infection. 23. A farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof for use in a method for treating or preventing a parasitic infection. 24. A farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor, or a pharmaceutically acceptable salt thereof, for use in a method for treating or preventing a Cryptosporidium infection. 25. A farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof for use in a method for treating or preventing a viral infection. 26. A farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof for use in a method for treating or preventing a rotavirus infection. 27. A farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof for use in a method for treating or preventing a bacterial infection. 28. A farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor, or a pharmaceutically acceptable salt thereof, for use in a method for treating or preventing a Salmonella infection. 29. The method according to any one of embodiments 1 to 14, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to embodiments 15 to 28, wherein the FDFT1 inhibitor is lapaquistat or a pharmaceutically acceptable salt thereof. 30. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 1 to 14, or embodiments 15 to 28, wherein the FDFT1 inhibitor has the following structure: [ka] 31. The method according to any one of embodiments 1 to 14, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to embodiments 15 to 28, wherein the FDFT1 inhibitor is YM-53601 or a pharmaceutically acceptable salt thereof. 32. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 1 to 14, or embodiments 15 to 28, wherein the FDFT1 inhibitor has the following structure: [ka] 33. The method according to any one of embodiments 1 to 14 or 29 to 32, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 32, wherein the FDFT1 inhibitor is administered simultaneously, sequentially or separately with one or more other drugs used in the treatment or prevention of parasitic infections or Cryptosporidium infections. 34. The method according to any one of embodiments 1 to 14 or 29 to 33, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 33, wherein the FDFT1 inhibitor is administered simultaneously, sequentially or separately with one or more other drugs used in the treatment or prevention of viral infections or rotavirus infections. 35. The method according to any one of embodiments 1 to 14 or 29 to 34, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 34, wherein the FDFT1 inhibitor is administered simultaneously, sequentially or separately with one or more other drugs used in the treatment or prevention of bacterial or Salmonella infections. 36. The method for use according to any one of embodiments 33 to 35, wherein one or more other drugs are formulated in a prepared state together with the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof. 37. The method for use according to any one of embodiments 33-36, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof, wherein the one or more other drugs comprise nitazoxanide, paromomycin, or halofuginone. 38. The method for use according to any one of embodiments 33-37, wherein the one or more other drugs comprises nitazoxanide, or a FDFT1 inhibitor or a pharmaceutically acceptable salt thereof. 39. The method according to any one of embodiments 1 to 14 or 29 to 38, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 38, wherein the FDFT1 inhibitor is administered to the patient orally, intravenously, intramuscularly, intrathecally, subcutaneously, sublingually, bucally, rectally, vaginally, ophthalmically, otorally, nasally, by inhalation, by spray, dermally, topically, or transdermally. 40. The method of any one of embodiments 1 to 14 or 29 to 39, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 39, wherein one or more other drugs are administered to the patient orally, intravenously, intramuscularly, intrathecally, subcutaneously, sublingually, buccally, rectally, vaginally, ophthalmically, otically, nasally, by inhalation, by spray, dermally, topically, or transdermally. 41. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 1 to 14 or 29 to 39, or any one of embodiments 15 to 40, wherein the subject is a human. 42. The method according to any one of embodiments 1 to 14 or 29 to 40, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 40, wherein the subject is a bovine (cattle), sheep, goat, cat, dog, porcine (pig), horse, or rabbit. 43. The method according to any one of embodiments 1 to 14 or 29 to 42, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 42, wherein the FDFT1 inhibitor is administered at a dose sufficient to achieve at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99% inhibition of FDFT1 activity. 44. The method according to any one of embodiments 1 to 14 or 29 to 43, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 43, wherein the FDFT1 inhibitor is administered at a dose sufficient to achieve at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99% inhibition of squalene production in target cells. 45. The method according to any one of embodiments 1 to 14 or 29 to 44, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 44, wherein the FDFT1 inhibitor prevents sexual development of the parasite. 46. ​​The method according to any one of embodiments 1 to 14 or 29 to 45, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 45, wherein the FDFT1 inhibitor reduces parasitic proliferation. 47. The method according to any one of embodiments 1 to 14 or 29 to 46, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 46, wherein the method comprises administering to the patient the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof at a dose of 0.0001 mg / kg to 100 mg / kg. 48. The method according to any one of embodiments 1 to 14 or 29 to 47, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 47, wherein the method comprises administering to the patient the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof at a dose of 0.01 mg / kg to 5 mg / kg. 49. The method according to any one of embodiments 1 to 14 or 29 to 48, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 48, wherein the method comprises administering to a patient a once-daily dose of the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof. 50. The method according to any one of embodiments 1 to 14 or 29 to 49, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 49, wherein the method comprises administering to a patient once daily a dose of the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof of 10 mg to 200 mg. 51. The method according to any one of embodiments 1 to 14 or 29 to 50, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 50, wherein the method comprises administering to a patient once daily a dose of the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof of 25 mg to 100 mg. 52. The method according to any one of embodiments 1 to 14 or 29 to 51, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 51, wherein the method comprises administering to the patient a dose of 25 mg, 50 mg, or 100 mg of the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof once daily. 53. The method according to any one of embodiments 1 to 14 or 29 to 52, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 52, wherein the method comprises administering to the patient once daily a dose of 25 mg, 50 mg, or 100 mg of lapaquistat or a pharmaceutically acceptable salt thereof. 54. The method according to any one of embodiments 1 to 14 or 29 to 52, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 52, wherein the method comprises administering to the patient a dose of 25 mg of lapaquistat or a pharmaceutically acceptable salt thereof once daily. 55. The method according to any one of embodiments 1 to 14 or 29 to 52, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 52, wherein the method comprises administering to the patient a dose of 50 mg of lapaquistat or a pharmaceutically acceptable salt thereof once daily. 56. The method according to any one of embodiments 1 to 14 or 29 to 52, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 52, wherein the method comprises administering to the patient a dose of 100 mg of lapaquistat or a pharmaceutically acceptable salt thereof once daily. 57. The method according to any one of embodiments 1 to 14 or 29 to 56, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 56, wherein the method further comprises determining whether the patient has a parasitic infection. 58. The method according to any one of embodiments 1 to 14 or 29 to 56, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 56, wherein the method further comprises determining whether the patient has a viral infection. 59. The method according to any one of embodiments 1 to 14 or 29 to 58, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 58, wherein the parasitic infection is an infection by an intracellular parasite incapable of endogenous cholesterol biosynthesis. 60. The method according to any one of embodiments 1 to 14 or 29 to 59, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 59, wherein the parasitic infection is an infection by an intracellular parasite incapable of endogenous squalene synthesis. 61. The method according to any one of embodiments 1 to 14 or 29 to 60, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 60, wherein the parasitic infection is an infection with an intracellular parasite that does not express endogenous squalene synthase. 62. The method according to any one of embodiments 1 to 14 or 29 to 61, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 61, wherein the parasitic infection is an infection with an intracellular parasite that is an obligate intracellular parasite. 63. The method according to any one of embodiments 1 to 14 or 29 to 62, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 62, wherein the parasitic infection is an infection with an intracellular parasite of the order Eucoccidiorida, preferably the suborder Eimeriorina. 64. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 1 to 14 or 29 to 63, or any one of embodiments 15 to 63, wherein the parasitic infection is an infection with a parasite that is a Cryptosporidium species. 65. The method according to any one of embodiments 1 to 14 or 29 to 64, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 64, wherein the FDFT1 inhibitor is administered simultaneously, sequentially or separately with one or more other drugs that inhibit cholesterol biosynthesis and / or reduce the amount of cholesterol in the subject's blood. 66. The method for use according to embodiment 65, wherein the one or more other drugs that inhibit cholesterol biosynthesis and / or reduce the amount of cholesterol in the subject's blood are statins, or FDFT1 inhibitors or pharmaceutically acceptable salts thereof. 67. The method for use according to embodiment 66, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof, wherein the statin is selected from one or more of lovastatin, atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin, preferably the statin is lovastatin or atorvastatin. 68. The method according to any one of embodiments 1 to 14 or 29 to 67, or the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of embodiments 15 to 67, wherein the FDFT1 inhibitor is lapaquistat and lapaquistat is administered in combination with lovastatin or atorvastatin. 69. Use of a therapeutically or prophylactically effective amount of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof in a method for treating or preventing a parasitic infection. 70. Use of a therapeutically or prophylactically effective amount of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof in a method for treating or preventing a Cryptosporidium infection. 71. Use of a therapeutically or prophylactically effective amount of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof in a method for treating or preventing a viral infection. 72. Use of a therapeutically or prophylactically effective amount of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof in a method for treating or preventing rotavirus infection. 73. Use of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof in a method for treating or preventing an infectious disease. 74. The use of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof according to embodiment 73, wherein the infection is an infection caused by a pathogen incapable of endogenous cholesterol biosynthesis. 75. The use of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof for use according to embodiment 73 or 74, wherein the infection is an infection caused by a pathogen incapable of endogenous squalene synthesis. 76. The use of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof according to any one of embodiments 73 to 75, wherein the infectious disease is an infection caused by a pathogen that does not express endogenous squalene synthase. 77. The use of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof according to any one of embodiments 73 to 76, wherein the infection is a parasitic, viral, or bacterial infection. 78. The use of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof according to embodiment 77, wherein the infection is a Cryptosporidium infection. 79. The use of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof according to embodiment 77, wherein the infection is a rotavirus infection. 80. The use of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof according to embodiment 77, wherein the infection is a Salmonella infection. 81. A pharmaceutical composition comprising a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof. 82. The pharmaceutical composition of embodiment 81, wherein the FDFT1 inhibitor is lapaquistat or YM53601. 83. The pharmaceutical composition of embodiment 81 or 82, wherein the composition further comprises a drug that inhibits cholesterol biosynthesis and / or reduces the amount of cholesterol in the subject's blood. 84. The pharmaceutical composition of embodiment 81 or 82, wherein the composition further comprises a statin. 85. The pharmaceutical composition of embodiment 84, wherein the statin is selected from the group consisting of lovastatin, atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin. 86. The pharmaceutical composition of embodiment 85, wherein the statin is selected from the group consisting of lovastatin and atorvastatin. 87. The composition comprises: a.FDFT1 inhibitors and statins, b. Lapaquistat and statins, c. Lapaquistat and lovastatin, d. Lapaquistat and atorvastatin, e.YM53601 and statins, f. YM53601 and lovastatin, or g. A pharmaceutical composition according to any one of embodiments 81 to 86, comprising YM53601 and atorvastatin. 88. A pharmaceutical composition according to any one of embodiments 81 to 87 for use in the treatment or prevention of intracellular infections. 89. The pharmaceutical composition for use according to embodiment 88, wherein the infectious disease is an infection caused by an intracellular pathogen incapable of endogenous cholesterol biosynthesis. 90. The pharmaceutical composition for use according to embodiment 88 or 89, wherein the infectious disease is an infection caused by an intracellular pathogen incapable of endogenous squalene synthesis. 91. The pharmaceutical composition for use according to embodiment 88, 89, or 90, wherein the infectious disease is an infection by an intracellular pathogen that does not express endogenous squalene synthase. 92. The pharmaceutical composition for use according to any one of embodiments 88 to 91, wherein the infectious disease is an intracellular parasitic, viral, or bacterial invention. 93. The pharmaceutical composition for use according to any one of embodiments 88-92, wherein the infection is an intracellular parasitic infection. 94. The pharmaceutical composition for use according to any one of embodiments 88-93, wherein the infection is a Cryptosporidium infection, a rotavirus infection, or a Salmonella infection. 95. The pharmaceutical composition for use according to any one of embodiments 88 to 94, wherein the infection is a Cryptosporidium infection. 96. A pharmaceutical composition according to any one of embodiments 81-87, wherein the composition further comprises one or more other drugs used in the treatment or prevention of parasitic infections, such as Cryptosporidium infections. 97. The pharmaceutical composition of any one of embodiments 81-87, wherein the composition further comprises nitazoxanide, paromomycin, or halofuginone. 98. The pharmaceutical composition of any one of embodiments 81-87, wherein the composition further comprises nitazoxanide. 99. The composition comprises: a. FDFT1 inhibitor and one or more of nitazoxanide, paromomycin, or halofuginone b. Lapaquistat and one or more of nitazoxanide, paromomycin, or halofuginone; c. YM53601 and one or more of nitazoxanide, paromomycin, or halofuginone; d. Lapaquistat and nitazoxanide, e.YM53601 and nitazoxanide, f. an FDFT1 inhibitor, a statin, and one or more of nitazoxanide, paromomycin, or halofuginone; g. lapaquistat, a statin, and one or more of nitazoxanide, paromomycin, or halofuginone; h. lapaquistat, lovastatin, and one or more of nitazoxanide, paromomycin, or halofuginone; i. lapaquistat, atorvastatin, and one or more of nitazoxanide, paromomycin, or halofuginone; j.YM53601, a statin, and one or more of nitazoxanide, paromomycin, or halofuginone; k. YM53601, lovastatin, and one of nitazoxanide, paromomycin, or halofuginone; l. YM53601, atorvastatin, and one of nitazoxanide, paromomycin, or halofuginone; m. Lapaquistat, statins, and nitazoxanide, n. Lapaquistat, lovastatin, and nitazoxanide, o. Lapaquistat, atorvastatin, and nitazoxanide p.YM53601, statins, and nitazoxanide, q.YM53601, lovastatin, and nitazoxanide, A pharmaceutical composition according to any one of embodiments 96 to 98, comprising r.YM53601, atorvastatin and nitazoxanide. 100. A pharmaceutical composition according to any one of embodiments 96 to 99 for use in the treatment or prevention of intracellular infections. 101. The pharmaceutical composition for use according to embodiment 100, wherein the infectious disease is an infection caused by an intracellular pathogen incapable of endogenous cholesterol biosynthesis. 102. The pharmaceutical composition for use according to embodiment 100 or 101, wherein the infectious disease is an infection caused by an intracellular pathogen incapable of endogenous squalene synthesis. 103. The pharmaceutical composition for use according to embodiment 100, 101, or 102, wherein the infectious disease is an infection by an intracellular pathogen that does not express endogenous squalene synthase. 104. A pharmaceutical composition for use according to any one of embodiments 100 to 103, wherein the infection is an intracellular parasitic infection. 105. A pharmaceutical composition for use according to any one of embodiments 100 to 104, wherein the infection is a Cryptosporidium infection. 106. A farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof, a. a drug that inhibits cholesterol biosynthesis and / or reduces the amount of cholesterol in a subject's blood, and / or b. In combination with one or more other drugs used in the treatment or prevention of parasitic infections. 107. The combination according to embodiment 106, wherein the FDFT1 inhibitor is lapaquistat or YM53601. 108. The combination according to embodiment 106 or 107, wherein the composition further comprises a drug that inhibits cholesterol biosynthesis and / or reduces the amount of cholesterol in the subject's blood. 109. A combination according to any one of embodiments 106-108, wherein the drug that inhibits cholesterol biosynthesis and / or reduces the amount of cholesterol in the subject's blood is a statin. 110. The combination according to embodiment 109, wherein the statin is selected from the group consisting of lovastatin, atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin. 111. The combination according to embodiment 109, wherein the statin is selected from the group consisting of lovastatin and atorvastatin. 112. The composition comprises: a.FDFT1 inhibitors and statins, b. Lapaquistat and statins, c. Lapaquistat and lovastatin, d. Lapaquistat and atorvastatin, e.YM53601 and statins, f. YM53601 and lovastatin, or g. A pharmaceutical composition according to any one of embodiments 106 to 111, comprising YM53601 and atorvastatin. 113. A combination according to any one of embodiments 106 to 112 for use in the treatment or prevention of intracellular infections. 114. The combination for use according to embodiment 113, wherein the infection is an infection caused by an intracellular pathogen incapable of endogenous cholesterol biosynthesis. 115. The combination for use according to embodiment 113 or 114, wherein the infection is an infection caused by an intracellular pathogen incapable of endogenous squalene synthesis. 116. A combination for use according to any one of embodiments 113 to 115, wherein the infection is an infection with an intracellular pathogen that does not express endogenous squalene synthase. 117. The combination for use according to any one of embodiments 113 to 116, wherein the infectious disease is an intracellular parasitic, viral or bacterial invention. 118. The combination for use according to any one of embodiments 113 to 117, wherein the infection is an intracellular parasitic infection. 119. The combination for use according to any one of embodiments 113 to 118, wherein the infection is a Cryptosporidium infection, a rotavirus infection, or a Salmonella infection. 120. A combination for use according to any one of embodiments 113-119, wherein the infection is a Cryptosporidium infection. 121. The combination according to any one of embodiments 106-112, wherein the combination further comprises one or more other drugs used in the treatment or prevention of parasitic infections, such as Cryptosporidium infections. 122. The combination of 112, wherein the one or more other drugs used in the treatment or prevention of parasitic infections is nitazoxanide, paromomycin, or halofuginone. 123. The combination embodiment 112, in which the one or more other drugs used in the treatment or prevention of parasitic infections is nitazoxanide. 124. The combination is a. FDFT1 inhibitor and one or more of nitazoxanide, paromomycin, or halofuginone b. Lapaquistat and one or more of nitazoxanide, paromomycin, or halofuginone; c. YM53601 and one or more of nitazoxanide, paromomycin, or halofuginone; d. Lapaquistat and nitazoxanide, e.YM53601 and nitazoxanide. f. an FDFT1 inhibitor, a statin, and one or more of nitazoxanide, paromomycin, or halofuginone; g. lapaquistat, a statin, and one or more of nitazoxanide, paromomycin, or halofuginone; h. lapaquistat, lovastatin, and one or more of nitazoxanide, paromomycin, or halofuginone; i. lapaquistat, atorvastatin, and one or more of nitazoxanide, paromomycin, or halofuginone; j.YM53601, a statin, and one or more of nitazoxanide, paromomycin, or halofuginone; k. YM53601, lovastatin, and one or more of nitazoxanide, paromomycin, or halofuginone; l. YM53601, atorvastatin, and one or more of nitazoxanide, paromomycin, or halofuginone; m. Lapaquistat, statins, and nitazoxanide, n. Lapaquistat, lovastatin, and nitazoxanide, o. Lapaquistat, atorvastatin, and nitazoxanide p.YM53601, statins, and nitazoxanide, q.YM53601, lovastatin, and nitazoxanide, r. A combination according to any one of embodiments 106 to 112 comprising YM53601, atorvastatin and nitazoxanide. 125. A combination according to any one of embodiments 121 to 124 for use in the treatment or prevention of intracellular infections. 126. The combination for use according to embodiment 125, wherein the infection is an infection caused by an intracellular pathogen incapable of endogenous cholesterol biosynthesis. 127. The combination for use according to embodiment 125 or 126, wherein the infection is an infection caused by an intracellular pathogen incapable of endogenous squalene synthesis. 128. A combination for use according to any one of embodiments 125-127, wherein the infection is an infection with an intracellular pathogen that does not express endogenous squalene synthase. 129. The combination for use according to any one of embodiments 125-128, wherein the infection is an intracellular parasitic infection. 130. A combination for use according to any one of embodiments 125-129, wherein the infection is a Cryptosporidium infection. 131. A combination according to any one of embodiments 106-112 or 121-124, or a combination for use according to any one of embodiments 113-120 or 125-130, wherein the components of the combination are for separate, simultaneous or sequential administration. 132. A kit comprising the components of any one of the combinations of embodiments 106-112 or 121-124. 133. The kit according to embodiment 132, wherein the components of the kit are placed separately in separate containers. 134. The kit of embodiment 132 or 133, further comprising instructions for use. 135. A statin for use in a method for treating or preventing an infection, wherein the statin is administered simultaneously, sequentially, or separately from a FDFT1 inhibitor or a pharmaceutically acceptable salt thereof. 136. A statin for use according to embodiment 135, further characterized by any one or more of the features of embodiments 1 to 134. 137. The statin for use according to embodiment 135 or embodiment 136, wherein the statin is lovastatin or atorvastatin. 138. The statin for use according to any one of embodiments 135 to 137, wherein the FDFT1 inhibitor is lapaquistat. 139. A statin for use according to any one of embodiments 135 to 138, wherein the infection is an infection with an intracellular parasite incapable of endogenous cholesterol biosynthesis, preferably wherein the parasite is a Cryptosporidium species. 135. A statin for use in a method for treating or preventing a Cryptosporidium infection, wherein the statin is lovastatin or atorvastatin and is administered simultaneously, sequentially, or separately with lapaquistat.

[0217] References [1]Use-case scenarios for an anti-Cryptosporidium therapeutic,Ashigbie PG et al.,PLoS Neglected Tropical Disease 2021 [2]A review of the global burden,novel diagnostics,therapeutics,and vaccine targets for Cryptosporidium.Checkley W et al.,Lancet Infectious Diseases 2015 [3]Ugawa,T.,Kakuta,H.,Moritani,H.,Matsuda,K.,Ishihara,T.,Yamaguchi,M.,Naganuma,S.,Iizumi,Y.and Shikama,H.(2000),YM-53601,a novel squalene synthase inhibitor,reduces plasma cholesterol and triglyceride levels in several animal species.British Journal of Pharmacology,131:63-70. [4]Amin,D.,S.A.Cornell,S.K.Gustafson,S.J.Needle,J.W.Ullrich,G.E.Bilder,and M.H.Perrone.Bisphosphonates used for the treatment of bone disorders inhibit squalene synthase and cholesterol biosynthesis.J.Lipid Res.1992.33:1657-1663. [5]Synthesis of Novel 4,1-Benzoxazepine Derivatives as Squalene Synthase Inhibitors and Their Inhibition of Cholesterol Synthesis; Takashi Miki,Masakuni Kori,Hiroshi Mabuchi,Ryu-ichi Tozawa,Tomoyuki Nishimoto,Yasuo Sugiyama,Koichiro Teshima,and Hidefumi Yukimasa Journal of Medicinal Chemistry 2002 45(20),4571-4580 [6]Inhibition of cholesterol synthesis by squalene synthase inhibitors does not induce myotoxicity in vitro.Flint OP et al.,Toxicology and Applied Pharmacology 1997 [7]Lipid-lowering properties of TAK-475,a squalene synthase inhibitor,in vivo and in vitro.Nishimoto T et al.,British Journal of Pharmacology 2003 [8]Development of a Squalene Synthase Inhibitor for the Treatment of Hypercholesterolemia.Stein EA et al.,Circulation 2011

Claims

1. A farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor, or a pharmaceutically acceptable salt thereof, for use in a method for treating or preventing a parasitic infection.

2. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to claim 1, wherein the parasitic infection is an infection caused by an intracellular parasite incapable of endogenous cholesterol biosynthesis.

3. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to claim 1 or 2, wherein the parasitic infection is an infection caused by an intracellular parasite incapable of endogenous squalene synthesis.

4. 10. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of the preceding claims, wherein the parasitic infection is an infection by an intracellular parasite that does not express endogenous squalene synthase.

5. 10. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of the preceding claims, wherein the parasitic infection is an infection by an intracellular parasite that is an obligate intracellular parasite.

6. 10. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of the preceding claims, wherein said parasitic infection is an infection by a parasite of the order Eucoccidiorida, preferably of the suborder Eimerioina.

7. 10. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of the preceding claims, wherein the parasitic infection is an infection caused by a Cryptosporidium species.

8. A farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor, or a pharmaceutically acceptable salt thereof, for use in a method for treating or preventing a Cryptosporidium infection.

9. A farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof for use in a method for treating or preventing a viral infection.

10. A farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof for use in a method for treating or preventing a rotavirus infection.

11. A farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor, or a pharmaceutically acceptable salt thereof, for use in a method for treating or preventing a bacterial infection.

12. A farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor, or a pharmaceutically acceptable salt thereof, for use in a method for treating or preventing a Salmonella infection.

13. 10. The FDFT1 inhibitor for use according to any one of the preceding claims, wherein said FDFT1 inhibitor has the structure: 【Chemical 1】

14. 10. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of the preceding claims, wherein said FDFT1 inhibitor is lapaquistat.

15. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of claims 1 to 12, wherein the FDFT1 inhibitor is YM-53601 or a pharmaceutically acceptable salt thereof.

16. 13. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of claims 1 to 12, wherein the FDFT1 inhibitor has the following structure: 【Chemistry 2】

17. 10. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of the preceding claims, wherein the FDFT1 inhibitor is administered simultaneously, sequentially or separately with one or more other drugs used in the treatment or prevention of the parasitic infection or Cryptosporidium infection.

18. 18. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to claim 17, wherein the one or more other drugs are formulated in a prepared state together with the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof.

19. 19. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to claim 17 or 18, wherein the one or more other drugs comprise nitazoxanide, paromomycin, or halofuginone.

20. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of claims 17 to 19, wherein the one or more other drugs include nitazoxanide.

21. FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of the preceding claims, wherein the FDFT1 inhibitor is administered simultaneously, sequentially or separately with one or more other drugs that inhibit cholesterol biosynthesis and / or reduce the amount of cholesterol in the subject's blood.

22. 22. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to claim 21, wherein the one or more other drugs that inhibit cholesterol biosynthesis and / or reduce the amount of cholesterol in the blood of the subject are statins.

23. 23. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to claim 22, wherein the statin is selected from one or more of lovastatin, atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin, preferably the statin is lovastatin or atorvastatin.

24. 10. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of the preceding claims, wherein the FDFT1 inhibitor is lapaquistat, and the lapaquistat is administered simultaneously, sequentially, or separately from lovastatin or atorvastatin.

25. 5. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of the preceding claims, wherein the FDFT1 inhibitor is administered to a patient orally, intravenously, intramuscularly, intrathecally, subcutaneously, sublingually, bucally, rectally, vaginally, ophthalmically, otorally, nasally, by inhalation, by spraying, dermally, topically, or transdermally.

26. 10. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of the preceding claims, wherein the subject is a human.

27. 26. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of claims 1 to 25, wherein the subject is a bovine (cattle), sheep, goat, cat, dog, porcine (pig), horse, or rabbit.

28. 10. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of the preceding claims, wherein the FDFT1 inhibitor is administered at a dose sufficient to achieve at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99% inhibition of FDFT1 activity.

29. 10. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of the preceding claims, wherein the FDFT1 inhibitor is administered at a dose sufficient to achieve at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99% inhibition of squalene production in target cells.

30. 10. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of the preceding claims, wherein said FDFT1 inhibitor prevents sexual development of said parasite.

31. 10. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of the preceding claims, wherein said FDFT1 inhibitor reduces the proliferation of said parasite.

32. 10. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of the preceding claims, wherein the method comprises administering to a patient the FDFT1 inhibitor or a pharmaceutically acceptable salt thereof at a dose of 0.0001 mg / kg to 100 mg / kg.

33. 10. The FDFT1 inhibitor or a pharmaceutically acceptable salt thereof for use according to any one of the preceding claims, wherein said method comprises administering to said patient once daily a dose of said FDFT1 inhibitor or a pharmaceutically acceptable salt thereof of 25 mg to 100 mg.

34. 1. Use of a therapeutically or prophylactically effective amount of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof in a method for treating or preventing a parasitic infection.

35. 1. Use of a therapeutically or prophylactically effective amount of a farnesyl diphosphate farnesyltransferase 1 (FDFT1) inhibitor or a pharmaceutically acceptable salt thereof in a method for treating or preventing a Cryptosporidium infection.

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