Methods and systems for predicting response of oral minoxidil to treat androgenetic alopecia

Abstract

The present invention relates to methods, processes, systems, and devices for predicting minoxidil response in the treatment of androgenetic alopecia, and based thereon the minoxidil dose amount, minoxidil dose frequency, and / or minoxidil dose routine prescription.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This patent application is related to and claims the benefit of priority of U.S. Provisional Patent Application No. 63 / 512,137, filed on July 6, 2023, the entire contents of which are incorporated herein by reference. Technical Field

[0003] The invention described herein relates to methods and systems for predicting the response to oral minoxidil treatment of androgenetic alopecia. Background Art

[0004] Hair loss is associated with a variety of psychological and social impacts. Before initiating any treatment, it would be advantageous to predict the course of the disease, its severity, and treatment options. In the area of ​​hair loss, there are currently very few scientific diagnostic tests available, and few methods for predicting treatment response.

[0005] Additionally, the hair loss industry is flooded with dozens of products claiming to grow, improve, and replace hair. Unfortunately, few treatments have been scientifically proven to be effective, and the few that undergo clinical trials are often not equally effective for all patients.

[0006] The drug minoxidil (known as Rogaine) is approved by the U.S. Food and Drug Administration (“FDA”) TM or Bio-Health TM (Rogaine TM or Regaine TM ) has been successfully used to treat androgenetic alopecia in men. Minoxidil is also FDA-approved for the treatment of hair loss in women; however, for most women, minoxidil is only marginally successful in preserving existing hair. Some men for whom minoxidil is less effective have been successfully treated with finasteride; however, the same cannot be said for women for whom minoxidil is ineffective. To date, studies have failed to show the effectiveness of finasteride in the treatment of androgenetic alopecia in women.

[0007] There are significant differences between androgenic alopecia in men and in women. In addition to the different patterns of baldness, hair loss in men and women follows different mechanisms. In men, hair loss is associated with the normal high androgen levels in men, combined with the underlying sensitivity of the hair roots to androgens. However, androgen levels in women are approximately 10 times lower than in men, and the absolute amount of androgens is a less important factor than the increased sensitivity of the hair roots to androgens.

[0008] There is a great deal of variability in how different individuals, both males and females, respond to various hair loss treatments. This variability is thought to be a result of genetic factors that lead to variable enzyme activity in the (hair) follicles, making a one-size-fits-all approach difficult to implement. It would therefore be advantageous to be able to have an effective diagnostic and therapeutic approach in which patients could be selected and treated based on criteria, such as enzyme activity, which would identify some individuals who might benefit from treatment with minoxidil and other drugs, while identifying other individuals for whom treatment is unlikely to be effective. Previous methods of predicting response to minoxidil are explained in U.S. Patent No. 8,691,518. However, there remains a need to predict the response to oral forms of minoxidil relative to topical forms of minoxidil. Summary of the invention

[0009] The invention described herein relates to systems and methods for predicting the response of oral and / or topical forms of minoxidil in the treatment of androgenetic alopecia, which in one embodiment can be based on a colorimetric assay. Various embodiments are possible, some of which are illustrated herein. In particular, changes in hair follicle minoxidil sulfotransferase activity can be used to predict the efficacy of minoxidil in the treatment of androgenetic alopecia.

[0010] In one embodiment of the present disclosure, a method for selecting a treatment for a subject with androgenetic alopecia is provided, comprising obtaining a sample or scalp biopsy of one or more hair follicles from the subject; performing a test to measure the minoxidil sulfotransferase activity in the sample, thereby generating an activity value indicating the level of minoxidil sulfotransferase activity in the sample; comparing the activity value to one or more standardized activity values, each of which represents a high or low expected minoxidil response to hair regrowth or retention for a class of patients including the subject, thereby generating an indication of a high or low expected minoxidil response to hair regrowth or retention for the subject at a specific dose of minoxidil; and presenting the indication to the subject. Optionally, the indication of a high or low expected minoxidil response to hair regrowth or retention is used to select an oral or topical minoxidil treatment.

[0011] In another embodiment, a composition of matter for use in detection is provided which comprises about 30 to about 70 mM potassium phosphate buffer (pH 6.5); about 3 to about 7 mM magnesium chloride; about 15 to about 25 μM adenosine 3',5'-diphosphate (PAP) or adenosine 3'-phosphate, 5'-phosphosulfate (PAPS); about 3 to about 7 mM p-nitrophenyl sulfate; and about 0.07 to about 0.13 mM minoxidil.

[0012] In another embodiment, a kit is provided, comprising a transparent container with a lid, the container containing the above-mentioned composition for performing the detection; a buffer container containing about 0.20M to about 0.30M Tris-HCl, pH 8.7; and a tool for mixing the contents of the buffer container with the contents of the device.

[0013] As will be explained herein, embodiments may relate to methods for selecting a treatment for a human subject suffering from androgenetic alopecia. The method may include obtaining a sample from the human subject. The sample may include one or more hairs plucked from the human subject. The one or more hairs may include one or more hair follicles. The method may include performing a colorimetric assay to measure minoxidil sulfotransferase activity in the sample, thereby generating an activity value indicative of the level of minoxidil sulfotransferase activity in the sample. In some embodiments, the step of placing the sample in a reaction mixture may include using an indicator dye and minoxidil. During the detection process, the indicator dye may undergo a color change associated with the amount of minoxidil sulfotransferase activity level in the sample. The activity value may be associated with the color change. The method may include comparing the activity value with one or more standardized activity values. Each standardized activity value may represent a high or low expected minoxidil response to hair regrowth or retention for a class of patients including the subject, thereby generating an indication of a high or low expected minoxidil response to hair regrowth or retention for the subject at a specific dose of minoxidil. The method may include presenting the indication to the human subject.

[0014] In some embodiments, the indication may be a high expected minoxidil response for hair regrowth or retention, and the specific dose of minoxidil may be selected from about 2% topical solution, about 5% topical solution, about 2% topical foam, about 5% topical foam, about 0.625 mg, 1.25 mg, 2.5 mg tablets, and about 5 mg tablets.

[0015] In some embodiments, the detection may include the following steps: placing the sample in a reaction mixture containing about 50 mM potassium phosphate buffer at a pH between about 6.5 and about 8.0, about 5 mM magnesium chloride, about 20 μM adenosine 3′,5′-diphosphate (PAP) or adenosine 3′-phosphate, 5′-phosphosulfate (PAPS), about 5 mM p-nitrophenyl sulfate, and about 0.1 mM minoxidil; mixing the reaction mixture containing the sample to initiate a reaction; incubating the sample in the reaction mixture for a predetermined length; and stopping the reaction.

[0016] In some embodiments, the potassium phosphate buffer can have a pH of about 8.0.

[0017] In some embodiments, a basic buffer of about 0.25 M Tris-HCl, pH about 8.7, can be added to the reaction mixture to quench the assay and improve the sensitivity of the assay.

[0018] In some embodiments, the reaction mixture can be incubated at about 37°C for about 30 minutes to about 24 hours.

[0019] In some embodiments, the sample within the reaction mixture can be incubated at room temperature.

[0020] In some embodiments, the reaction mixture can be incubated above room temperature to increase dye turnover and signal intensity of colorimetric assays.

[0021] In some embodiments, the reaction mixture can be packaged in a capsule and dissolved in solution along with the sample.

[0022] In some embodiments, one or more standard values ​​can be one or more minoxidil sulfotransferase activity levels at which a statistical sample of other subjects show a high or low minoxidil response to hair regrowth or retention at a particular dose of minoxidil.

[0023] In some embodiments, the step of presenting may include sending an electronic signal.

[0024] In some embodiments, the indicator dye can be p-nitrophenyl sulfate.

[0025] In some embodiments, colorimetric assays can use 2-naphthol as a substrate to improve the sensitivity or specificity of detection.

[0026] In some embodiments, the sample may consist of a single hair plucked from a human subject, the hair comprising a single hair follicle.

[0027] In some embodiments, the reaction time for detection can be inversely proportional to the number of follicles in the reaction.

[0028] In some embodiments, a human subject with high minoxidil sulfotransferase activity may be prescribed a lower dose of minoxidil and / or a less frequent minoxidil application.

[0029] In some embodiments, a human subject with low minoxidil sulfotransferase activity may be prescribed a higher dose of minoxidil and / or an increased frequency of minoxidil administration.

[0030] In some embodiments, a human subject having low minoxidil sulfotransferase activity may be prescribed a stabilized form of minoxidil sulfate in the form of a cream, solution, and / or gel.

[0031] In some embodiments, minoxidil sulfate can be stabilized in liposomes or microcapsules.

[0032] In some embodiments, the assay may include positive (reference) and negative (blank) controls to compare the sample to.

[0033] In some embodiments, the color change can be visually discernible.In some embodiments, the detection can be performed in a transparent container.

[0034] In some embodiments, an activity value can be generated by comparing the discernible color after the color change to a reference color chart.

[0035] In some embodiments, colorimetric assays can be performed in a transparent container and activity values ​​generated by measuring absorbance at approximately 405 nm with a spectrophotometer.

[0036] Another exemplary embodiment may be directed to a method for predicting a response to minoxidil. The method may include measuring a gene, genetic and / or enzyme activity in a sample of a patient to generate an activity value indicative of a biochemical activation response to minoxidil. The method may include comparing the activity value to a standardized activity value. The method may include predicting a response to minoxidil treatment based on the comparison.

[0037] In some embodiments, measuring gene or enzyme activity can include: measuring SULT1A1 gene expression, SULT1A1 gene variant expression and / or SULT1A1 enzyme activity in a sample; measuring SLC22A9 gene expression, SLC22A9 gene variant expression, SLC22A9 transport activity from hair cells and / or SLC22A9 transporter activity in a sample; measuring AABC3 gene expression and / or AABC3 gene variant expression in a sample; and / or measuring blood flow in a patient (e.g., a patient's scalp).

[0038] In some embodiments, SLC22A9 transport activity from hair cells can be measured using a standard substrate uptake assay with a known substrate (e.g., a fluorescent substrate, a radionuclear substrate, etc.)

[0039] In some embodiments, minoxidil treatment can be oral minoxidil.

[0040] In some embodiments, predicting a response to minoxidil treatment may include:

[0041] - when the gene, genetics and / or enzyme activity involves SULT1A1: when the activity value is below the threshold normalized activity value, the patient is estimated to respond to oral minoxidil, and when the activity value is above the threshold normalized activity value, the patient is estimated to respond poorly to oral minoxidil;

[0042] - when SLC22A9 is involved in gene, inheritance and / or SLC22A9 transporter activity: when the activity value is above the threshold normalized activity value, it is estimated that the patient will respond to oral minoxidil, and when the activity value is below the threshold normalized activity value, it is estimated that the patient will not respond well to oral minoxidil;

[0043] - When the gene and / or genetic activity involves AABC3: when the activity value is below the threshold standardized activity value, it is estimated that the patient will respond to oral minoxidil, and when the activity value is above the threshold standardized activity value, it is estimated that the patient will respond poorly to oral minoxidil.

[0044] In some embodiments, measuring the patient's blood flow (e.g., the patient's scalp) can include Doppler velocity measurement. Predicting the response to minoxidil treatment can include: estimating that the patient will respond well to oral minoxidil when the Doppler velocity is below a threshold; and estimating that the patient will respond poorly to oral minoxidil when the Doppler velocity is above a threshold.

[0045] In some embodiments, when the gene, genetic and / or enzyme activity involves SULT1A1: when the activity value is below a threshold standardized activity value in the range of 0.37 to 0.4, it is estimated that the patient will respond well to oral minoxidil; and when the activity value is above a threshold standardized activity value in the range of 0.37 to 0.4, it is estimated that the patient will respond poorly to oral minoxidil.

[0046] In some embodiments, minoxidil treatment can be a treatment for androgenetic alopecia.

[0047] In some embodiments, the method may include generating a plurality of activity values ​​indicative of a biochemical activation response to minoxidil; and comparing the plurality of activity values ​​to a plurality of standard activity values.

[0048] In some embodiments, the response to minoxidil treatment can be increased or improved hair growth or hair retention.

[0049] In some embodiments, predicting a response to minoxidil treatment can include estimating a biochemical activation response based on a minoxidil dosage amount, a minoxidil dosage frequency, and / or a minoxidil dosage routine.

[0050] In some embodiments, the normalized activity value may be related to the biochemical activation response to minoxidil associated with hair growth or hair retention in a class of individuals.

[0051] In some embodiments, the normalized activity value can relate to a biochemical activation response to minoxidil associated with hair growth or hair retention, wherein a statistical sample of subjects shows a high or low minoxidil response to minoxidil dosage amount, minoxidil dosage frequency, and / or minoxidil dosage routine.

[0052] In some embodiments, measuring gene, genetic, and / or enzyme activity in a sample from a patient may include obtaining one or more hair follicles and / or one or more scalp biopsies as a sample.

[0053] In some embodiments, gene, genetic and / or enzymatic activity can be measured in a sample from a patient before, during, and / or after minoxidil treatment is administered to the patient.

[0054] In some embodiments, gene, genetic and / or enzyme activity can be measured in a sample from a patient 1 to 14 days prior to administering minoxidil treatment to the patient.

[0055] In some embodiments, measuring genetic, hereditary and / or enzymatic activity in a patient's sample can be performed by a detection device.

[0056] In some embodiments, measuring genetic, hereditary and / or enzymatic activity in a patient's sample can be performed by a colorimetric assay device.

[0057] In some embodiments, predicting response to minoxidil treatment may include implementation of a neural network.

[0058] In some embodiments, measuring the gene, genetic and / or enzyme activity in a sample from a patient may include obtaining one or more hair follicles and / or one or more scalp biopsies as a sample, and measuring the gene, genetic and / or enzyme activity in the sample from the patient is performed by a detection device, wherein the method includes: placing the one or more hair follicles or one or more scalp biopsies in a reaction mixture containing potassium phosphate buffer, magnesium chloride, adenosine 3',5'-diphosphate (PAP) or adenosine 3'-phosphate, 5'-phosphosulfate (PAPS), p-nitrophenyl sulfate and minoxidil; mixing the reaction mixture; incubating the reaction mixture for a predetermined period of time; and stopping the reaction.

[0059] Another exemplary embodiment may be directed to a method for selecting a treatment for a human subject suffering from androgenetic alopecia. The method may include measuring genetic, hereditary and / or enzymatic activity in a sample of the patient to produce an activity value indicative of a biochemical activation response to minoxidil. The method may include comparing the activity value to a standardized activity value. The method may include predicting a response to minoxidil treatment based on the comparison. The method may include prescribing a minoxidil dosage amount, a minoxidil dosage frequency and / or a minoxidil dosage routine prescription as a treatment for androgenetic alopecia.

[0060] In some embodiments, measuring genetic, genetic and / or enzyme activity can include: measuring SULT1A1 gene expression, SULT1A1 gene variant expression and / or SULT1A1 enzyme activity in a sample; measuring SLC22A9 gene expression, SLC22A9 gene variant expression, SLC22A9 activity and / or SLC transporter activity from hair follicles in a sample; measuring AABC3 gene expression and / or AABC3 gene variant expression in a sample; and / or measuring blood flow in a patient.

[0061] In some embodiments, prescribing a minoxidil dosage amount, a minoxidil dosage frequency, and / or a minoxidil dosage routine can include prescribing oral minoxidil.

[0062] In some embodiments, measuring the patient's blood flow (the patient's scalp) can include Doppler velocity measurement. Predicting the response to minoxidil treatment can include: when the Doppler velocity is below a threshold, estimating that the patient will respond well to oral minoxidil; and when the Doppler velocity is above a threshold, estimating that the patient will respond poorly to oral minoxidil.

[0063] In some embodiments, predicting a response to minoxidil treatment may include:

[0064] - when the gene, genetic and / or enzyme activity involves SULT1A1: when the activity value is below the threshold normalized activity value, it is estimated that the patient will respond to oral minoxidil; and when the activity value is above the threshold normalized activity value, it is estimated that the patient will not respond well to oral minoxidil;

[0065] - when SLC22A9 is involved in the genetic, hereditary and / or hair cell derived SLC22A9 transporter activity: when the activity value is above the threshold normalized activity value, it is estimated that the patient will respond to oral minoxidil; and when the activity value is below the threshold normalized activity value, it is estimated that the patient will not respond well to oral minoxidil;

[0066] - When the gene and / or genetic activity involves AABC3: when the activity value is below the threshold standardized activity value, it is estimated that the patient will respond to oral minoxidil; and when the activity value is above the threshold standardized activity value, it is estimated that the patient will respond poorly to oral minoxidil.

[0067] In some embodiments, when the gene, genetic and / or enzyme activity involves SULT1A1: when the activity value is below a threshold standardized activity value in the range of 0.37 to 0.4, it is estimated that the patient will respond well to oral minoxidil; and when the activity value is above a threshold standardized activity value in the range of 0.37 to 0.4, it is estimated that the patient will respond poorly to oral minoxidil. BRIEF DESCRIPTION OF THE DRAWINGS

[0068] The accompanying drawings incorporated in this specification illustrate one or more exemplary embodiments of the invention disclosed herein, and together with the specific embodiments, are used to explain the principles and exemplary implementations of these inventions. It will be understood by those skilled in the art that the accompanying drawings are only illustrative, and the contents depicted therein can be adjusted based on the text of the specification or common knowledge in the art.

[0069] In the drawings, the same reference numerals refer to the same reference numerals in the specification:

[0070] Figure 1 is a flow chart illustrating a method of analyzing one or more hair follicles and providing results.

[0071] Figure 2 An example of a computerized system for performing or analyzing an assay to test hair follicles and providing results is shown.

[0072] Figure 3 A flow chart for the sulfonation of minoxidil is shown. DETAILED DESCRIPTION

[0073] Various exemplary embodiments of the invention are described herein in the context of treating androgenetic alopecia.

[0074] The description herein is provided in the context of treatment of androgenetic alopecia. One of ordinary skill in the art will recognize that the following detailed description is illustrative only and is not intended to be limiting in any way. Other embodiments will readily suggest themselves to those of skill having the benefit of this disclosure. Reference will now be made in detail to the embodiments illustrated in the accompanying drawings. Throughout the drawings and the following detailed description, the same reference indicators will be used to refer to the same or similar parts.

[0075] For the sake of clarity, not all routine features of the implementations described herein are shown and described. Of course, it will be appreciated that in the development of any such actual implementation, many implementation-specific decisions must be made in order to achieve the developer's specific goals, such as compliance with application and business-related constraints, and that these specific goals will vary from implementation to implementation and developer to developer. Furthermore, it will be appreciated that such development work may be complex and time-consuming, but is still a routine task of engineering for those of ordinary skill in the art having the benefit of this disclosure.

[0076] Androgenetic alopecia is extremely common, affecting approximately 60% of men and more than 50% of women by the age of 60. Currently, there are two FDA-approved drugs for the treatment of androgenetic alopecia, finasteride and minoxidil. However, finasteride therapy, which is successful in hair regrowth and maintenance in men, has failed to show significant improvement in women. Therefore, minoxidil is currently the only FDA-approved drug for the treatment of female hair loss. In addition, in order for minoxidil therapy to be effective, it must usually be used for a long time without knowing whether it is effective. One object of the present invention is to screen patients before the start of treatment and / or during treatment to determine which patients respond best to minoxidil treatment, and further determine the form of minoxidil that patients respond best to (e.g., topical or oral), thereby providing personalized and effective treatment for hair loss.

[0077] The present invention is based in part on the discovery that minoxidil requires biochemical activation by the enzyme minoxidil sulfotransferase or SULT1A1 to form an active minoxidil sulfate metabolite. The exact mechanism of action of minoxidil for the treatment of androgenetic alopecia is not fully understood. However, in vitro studies have demonstrated that minoxidil sulfate is an active metabolite of minoxidil. The response of minoxidil for the treatment of androgenetic alopecia is associated with differences in scalp sulfotransferase activity. Therefore, it is generally believed that subjects with high levels of minoxidil sulfotransferase activity will produce more minoxidil sulfate and may therefore respond well to minoxidil for the treatment of androgenetic alopecia. On the other hand, subjects with low levels of minoxidil sulfotransferase activity will not produce large amounts of minoxidil sulfate and may respond poorly to minoxidil for the treatment of androgenetic alopecia.

[0078] Clinical trials using minoxidil to treat androgenetic alopecia have shown statistically significant results for hair maintenance and growth. Several studies have demonstrated that minoxidil sulfotransferase activity levels are significantly higher in patients who respond to minoxidil treatment for androgenetic alopecia. As described herein, hair regrowth is assessed based on one or more of the following parameters: patient self-assessment, physician assessment using a standardized scale, global photographic assessment, hair diameter measurement, average hair length measurement, average hair diameter measurement, and hair weight measurement. The present invention provides a method for using biochemical changes in minoxidil sulfotransferase activity as a marker of drug response for oral and / or topical minoxidil treatment of androgenetic alopecia. Based on the level of minoxidil sulfotransferase activity, the methods disclosed herein allow a physician or patient to select an appropriate treatment method and its dosage to treat androgenetic alopecia.

[0079] According to a method described herein, a hair follicle sample can be obtained from a patient. Preferably, at least two hair follicles can be obtained so that if only one is analyzed, there will be at least one backup if necessary. In one embodiment, the hair follicle sample is collected before starting minoxidil treatment. In another embodiment, the hair follicle sample is collected after starting minoxidil treatment.

[0080] The patient's hair follicle sample can be subjected to a colorimetric assay to determine the level of minoxidil sulfotransferase activity. The patient's hair follicle sample (from 1 to n follicles) can be placed in a reaction mixture containing about 50 mM potassium phosphate buffer (pH about 6.5), about 5 mM magnesium chloride, about 20 μM adenosine 3',5'-diphosphate (PAP) or adenosine 3'-phosphate, 5'-phosphosulfate (PAPS), about 5 mM p-nitrophenyl sulfate, and about 0.1 mM minoxidil.

[0081] In one embodiment, the reaction can be carried out in a transparent container with a lid or other opening into which the hair follicle sample can be inserted. In one non-limiting example, the total amount of liquid in the test container can be about 0.2 ml.

[0082] As part of the above reaction, it will be appreciated that in the presence of minoxidil sulfotransferase activity, p-nitrophenyl sulfate is converted to a colorimetric p-nitrophenolate.

[0083] Depending on the number of follicles used in the assay, the reaction can be mixed and then incubated at 37°C for about 4 to 16 hours. Mixing can be performed by any mixing means known in the art, including shaking the container. Wherein a shorter incubation time is required for a greater number of follicles. In one embodiment, an assay using one follicle can be incubated for about 16 hours. In another embodiment, an assay using two follicles can be incubated for about four hours.

[0084] After the sample incubation, the reaction can be stopped by adding about 1 / 10 volume of about 0.25M Tris-HCl buffer, pH 8.7 and mixing. The pH value can vary, and in one embodiment is between 8.5 and 9.0. In particular, if detection is performed or sold as a part of a test kit, an alkaline buffer can be provided as a separate container for pouring into the detection reaction vessel. In another embodiment, the alkaline buffer can be provided in a pre-installed syringe and injected into the main reaction vessel at the appropriate time by manually pushing the plunger or by some automatic or computerized control.

[0085] The absorbance at about 405 nm can then be read with a spectrophotometer, or compared to a reference color chart having an intensity range corresponding to the minoxidil sulfotransferase activity. Patients with relatively high levels of sulfotransferase activity will have relatively strong colorimetric readings, resulting in relatively significant color changes. In contrast, patients with relatively low levels of sulfotransferase activity will have relatively weak colorimetric readings, with correspondingly relatively small color changes. Patients with strong colorimetric assay reactions are expected to respond to minoxidil hair regeneration or retention. However, patients with weak colorimetric assay reactions are expected to respond poorly to minoxidil.

[0086] In yet another embodiment, the results from the colorimetric assay of the patient's hair follicles are used to determine the best treatment regimen. This includes determining the method of delivering minoxidil (oral vs. topical), or changing the concentration and / or frequency of minoxidil treatment to accommodate the patient's minoxidil sulfotransferase activity. Additionally, if the patient is unlikely to respond to minoxidil, finasteride may be recommended as an alternative to minoxidil.

[0087] refer to Figure 1, the method 100 described herein includes, at 102, collecting a hair follicle sample from a subject. The collection may be performed before and / or after the start of minoxidil treatment. Then, at 104, the hair follicle sample may be encoded with a unique identifier, for example, to protect privacy and facilitate handling. At 106, the hair follicle sample may be analyzed as described above. The analysis may be performed using the colorimetric assay described herein. Then, at 108, the results of the analysis may be provided to the subject or the subject's caregiver. The results of the analysis, each associated with its unique identifier, may be transmitted to a computer system, which may include a web-based server that is accessible to the subject or caregiver through appropriate authentication, for example, using the unique identifier. The results may include a prediction of the required dose and daily treatment frequency by comparing the patient's minoxidil sulfotransferase activity level to a reference database, in addition to providing an indication of the likelihood that the patient will respond to 2%, 5% or more minoxidil for the treatment of androgenetic alopecia. The results will also provide an indication of the likelihood that the patient will respond to oral or topical minoxidil for the treatment of androgenetic alopecia.

[0088] Figure 2 A system 200 for implementing the above-described procedures is schematically shown. A sample 202 of hair follicles from a subject is sent to a laboratory 204. The sample is then analyzed according to one or more of the above-described procedures. For example, the results of the analysis are compared with a database to generate an indication of the likelihood that the patient will respond to oral or topical application of minoxidil to treat androgenetic alopecia. The database can be dynamic in nature, constantly updated based on past minoxidil treatments and responses thereto for statistical adaptation, so that the database can adapt or learn from the patient pool and treatment over time, and in this way become a better predictor of the likelihood of responders to drug treatment. A database or other entity or circuit or module capable of performing the adaptive scheme described herein can reside in a computer system 206, or be separate from the computer system 206. The results of the comparison and analysis can be forwarded to a computer system 208 of the subject or caregiver, for example, electronically forwarded via a network, such as the Internet 210. Alternatively or additionally, the results of the comparison and analysis can be stored on a server 212 for remote access by the subject or caregiver after appropriate authentication, which may require reference to a unique identifier to protect privacy.

[0089] Table 1 below shows the results of testing patients for responsiveness to minoxidil. In one embodiment, the test is performed by placing hair follicles in a test. The hair follicles can be collected before minoxidil treatment or after minoxidil treatment has begun. The follicles are placed in a solution containing minoxidil. The test is then performed as described above and checked to determine if there is a SULT1A1 response. The results are then used as a predictor for patients who will respond well to minoxidil, and for patients who will respond better to oral minoxidil than topical minoxidil. Table 1 shows the raw data values ​​for the response to the test. The first column is the optical density produced by the colorimetric test. The second column represents the response. The test showed that the method used to predict oral (tablet) response cannot be used to predict the response to topical minoxidil.

[0090] The tests showed that low sulfotransferase activity was significantly associated with response to topical minoxidil. Therefore, low SULT1A1 expression is a predictor that a patient will respond well to topical minoxidil. Conversely, high sulfotransferase activity was associated with a low likelihood of response to oral minoxidil for androgenetic alopecia. Therefore, high SULT1A1 expression is a predictor that a patient will not respond well to oral minoxidil.

[0091] Table 1

[0092]

[0093]

[0094] Tests have shown a correlation between high SULT1A1 expression in hair follicles when exposed to minoxidil and a lower likelihood of responding well to oral minoxidil. It is believed that this is because when the oral form is used, suffocation occurs in the liver and the minoxidil dissolves in the tissues.

[0095] Additionally or alternatively, the test can be used to examine genetic variations in the SULT1A1 gene, whereby variants predisposing to low SULT1A1 expression can be used to predict response to minoxidil treatment route, minoxidil treatment dose, and treatment frequency, or a combination thereof.

[0096] The system and method can also be implemented using a neural network to predict the likelihood that a patient will respond to minoxidil for the treatment of androgenetic alopecia based on the patient's minoxidil sulfotransferase activity profile. According to such a method, predicting the likelihood of response to drug treatment can include (a) constructing an N-layer neural network, and (b) training the neural network using a dataset of the patient's outcome of treatment of androgenetic alopecia with minoxidil along with the patient's minoxidil sulfotransferase activity profile, (c) obtaining a hair follicle sample from the subject, (d) generating a minoxidil sulfotransferase activity profile from the sample that is a function of values ​​associated with a prescription set of minoxidil sulfotransferase activity levels; (e) inputting the subject's minoxidil sulfotransferase activity profile into the neural network; (f) obtaining a value or set of values ​​from the neural network that indicates the patient's expected outcome (responder) to a single dose or multiple doses of drug treatment; and (g) providing the patient with a recommended dose of drug treatment.

[0097] It can be understood from the present disclosure that embodiments may relate to a method for predicting a response to minoxidil. The method may include measuring sulfotransferase activity in a sample of a patient to produce an activity value indicative of a biochemical activation response to minoxidil. In some cases, measuring sulfotransferase activity may include measuring SULT1A1 gene expression and / or SULT1A1 gene variant expression in the sample. Measuring sulfotransferase activity in a sample of a patient may include obtaining one or more hair follicles and / or one or more scalp biopsies as a sample. For example, the sample may be subjected to a colorimetric assay to determine the level of sulfotransferase activity. For example, measuring sulfotransferase activity in a sample of a patient may include obtaining one or more hair follicles and / or one or more scalp biopsies as a sample, and measuring sulfotransferase activity in the sample of the patient by a detection device, wherein the method comprises:

[0098] i. placing one or more hair follicles or one or more scalp biopsies in a reaction mixture containing potassium phosphate buffer, magnesium chloride, adenosine 3',5'-diphosphate (PAP) or adenosine 3'-phosphate, 5'-phosphosulfate (PAPS), p-nitrophenyl sulfate and minoxidil;

[0099] ii. mixing the reaction mixture; incubating the reaction mixture for a predetermined period of time; and

[0100] iii. Stop the reaction.

[0101] As a non-limiting example, a patient's hair follicle sample (from 1 to n hair follicles) can be placed in a reaction mixture containing about 50 mM potassium phosphate buffer (pH about 6.5), about 5 mM magnesium chloride, about 20 μM adenosine 3',5'-diphosphate (PAP) or adenosine 3'-phosphate, 5'-phosphosulfate (PAPS), about 5 mM p-nitrophenyl sulfate, and about 0.1 mM minoxidil. The reaction can be carried out in a transparent container with a lid or other opening into which the hair follicle sample can be inserted.

[0102] As part of the above reaction, it should be understood that in the presence of minoxidil sulfotransferase activity, p-nitrophenyl sulfate is converted into a colorimetric p-nitrophenolate / root. The absorbance at about 405 nm can then be read with a spectrophotometer, or compared with a reference color card having an intensity range corresponding to the minoxidil sulfotransferase activity. Patients with relatively high levels of sulfotransferase activity will have relatively strong colorimetric readings, resulting in relatively significant color changes. In contrast, patients with relatively low levels of sulfotransferase activity will have relatively weak colorimetric readings, and correspondingly relatively small color changes. The intensity of the colorimetric reading can be quantified-for example, a very weak reading (or weak intensity) can be assigned an activity value of 0, while a very strong reading (or strong intensity) can be assigned an activity value of 1. The gradual change in the reading can be assigned a value between 0 and 1. The scale of 0 to 1 is used for exemplary purposes.

[0103] It should be noted that the sulfotransferase activity in the patient's sample can be measured before (e.g., 1-14 days before), during and / or after minoxidil treatment is administered to the patient. Therefore, the methods disclosed herein are not limited to measuring sulfotransferase activity during or after minoxidil treatment.

[0104] The method may involve comparing the activity value with a standardized activity value. The standardized activity value may be determined based on empirical data obtained from multiple subjects who have undergone minoxidil treatment and their responses measured. For example, the comparison may be performed by comparing the activity value with a lookup table containing multiple standardized activity values. The response to minoxidil treatment may be predicted based on the comparison.

[0105] In some embodiments, minoxidil treatment can be a treatment for androgenetic alopecia. The response to minoxidil treatment can be increased or improved hair growth or hair retention. Predicting the response to minoxidil treatment can include estimating the response based on minoxidil dosage amount, minoxidil dosage frequency, and / or minoxidil dosage routine.

[0106] As described herein, the minoxidil treatment can be oral minoxidil or topical minoxidil. It is also noted herein that low SULT1A1 gene expression and / or SULT1A1 gene variant expression (or low activity) can be a predictor that a patient will respond well to topical minoxidil treatment. High SULT1A1 gene expression and / or SULT1A1 gene variant expression (or high activity) can be a predictor that a patient will respond poorly to oral minoxidil treatment. Thus, predicting a response to minoxidil treatment can include estimating that a patient will respond well to topical minoxidil when the activity value is below a threshold standardized activity value, and estimating that a patient will respond poorly to oral minoxidil when the activity value is above a threshold standardized activity value. The threshold value will depend on the empirical data collected, the category of the individual (e.g., male, female, race, type of hair loss, etc.), how the data is trained (if data training is performed), etc. It should be understood that the standardized activity value can relate to a biochemical activation response to minoxidil associated with hair growth or hair retention for one or more individual categories. In some cases, this may involve gene expression and / or SULT1A1 gene variant expression associated with hair growth or hair maintenance for one or more individual categories. Thus, the comparison may take into account the individual category to which the patient from whom the sample was collected belongs. The patient may belong to one or more individual categories. Some embodiments may include generating multiple activity values ​​indicating a biochemical activation response to minoxidil (which, in some embodiments, may indicate gene expression and / or SULT1A1 gene variant expression in the sample), and comparing the multiple activity values ​​to multiple standardized activity values. In an exemplary embodiment, the standardized activity value may involve a biochemical activation response to minoxidil associated with hair growth or hair maintenance, wherein a statistical sample of subjects shows a high or low minoxidil response to minoxidil dosage amount, minoxidil dosage frequency, and / or minoxidil dosage routine.

[0107] In some embodiments, genetic testing of SLC family genes (e.g., the SLC22A9 gene) can be used to predict response to minoxidil treatment. Genetic testing of one or more genes in the SLC family can produce results that predict low SLC activity or expression. For example, a prediction of low activity or expression of one or more genes in a patient's SLC family can be an indicator that there is or will be a low oral minoxidil response. A prediction of high activity or expression of one or more genes in a patient's SLC family can be an indicator that there is or will be a high oral minoxidil response.

[0108] In some embodiments, gene detection of AABC family genes (e.g., AABC3 genes) can be used to predict the response to minoxidil treatment. Gene detection of one or more genes in the AABC family can produce results that predict high AABC activity or expression. For example, the prediction of high activity or expression of one or more genes in the patient's AABC family can be an indicator of the presence or absence of a low oral minoxidil response. The prediction of low activity or expression of one or more genes in the patient's AABC family can be an indicator of the presence or absence of a high oral minoxidil response.

[0109] It will be appreciated that gene or genetic activity or expression may include the activity or expression of protein, mRNA, DNA, and the like.

[0110] In some embodiments, blood flow in the patient's skin (e.g., scalp) can be detected by Doppler velocimetry (LDV), optical pulse plethysmography, near-infrared imaging, thermal imaging, optical coherence tomography, orthogonal polarization spectral imaging, fluorescence imaging, laser Doppler imaging, microscopy, spatial frequency domain imaging, photoacoustic detection, spectral imaging, hyperspectral imaging, and electromagnetic induction. (One or more) alternative measurements such as tissue oxygenation can also be used to measure blood flow. Blood flow in the skin can be used as an indicator to predict the effectiveness of minoxidil in treating hair loss. The details of the relationship between blood flow and minoxidil efficacy can be understood from International Application Publication No. WO2017007921, which is incorporated herein by reference in its entirety. For embodiments using Doppler technology, a lower Doppler velocity can be an indication of a high oral minoxidil response to minoxidil and / or a low local minoxidil response.

[0111] Example

[0112] Data Overview

[0113] A total of 123 subjects were recruited. Overall, among subjects with OD<0.37, 85% responded to oral minoxidil (5 mg for men and 1.25 mg for women). Overall, among subjects with OD>0.37, 43% responded to oral minoxidil (5 mg for men and 1.25 mg for women). This was statistically significant p=0.0088 (Fischer Exact Test). In this cohort, oral minoxidil was only effective for 42% of women and 73% of men.

[0114] discuss

[0115] This study supports the use of assays (e.g., Mediator Release Test (MRT) assays) to differentiate responders from non-responders to oral minoxidil; however, the effects of oral minoxidil have been found to be opposite to those of topical minoxidil for the treatment of androgenetic alopecia, i.e., lower SULT1A1 enzyme activity in hair follicles predicted oral minoxidil response. This is a significant and unexpected finding, as it suggests that oral minoxidil is sulfonated in the liver, but response is determined by the influx transporter SLC22A9 in the hair follicle. High or low activity of SULT1A1 in the hair follicle is an indirect marker of transporter expression. Patients with high SULT1A1 expression in the hair follicle have correspondingly high expression of the ABCC3 efflux transporter and low expression of the SLC22A9 influx transporter; thus resulting in a low response to oral minoxidil. The opposite is true for patients with low SULT1A1 expression in the hair follicle (see Figure 3 ).

[0116] Classification models / techniques, artificial intelligence, etc. can be used to predict the response to minoxidil treatment. For example, the empirical data of standardized activity values ​​can be a training data set stored in a data storage (e.g., a database). The classification model can be implemented on a processor (e.g., a computer device) to compare (one or more) activity values ​​with standardized activity values ​​and / or predict or estimate the minoxidil treatment response. When developing a standardized data set, activity data can be obtained from one or more individuals to generate a robust data set, which can allow the model to be used to determine trends, predict reaction states, use multivariate analysis of conditions and factors (e.g., race, age, sex, type of alopecia, minoxidil dosage, minoxidil dosage frequency, minoxidil dosage routine, etc.) that cause or involve reactions, etc. For example, multivariate modeling techniques can be used to determine which conditions or factors statistically contribute to reactions, reaction changes, etc. Multivariate modeling techniques may include one or more of the following: logistic regression with or without cubic splines, random forests, xgboost, support vector machines, nearest neighbors, artificial neural networks and / or long short-term memory (LSTM), multivariate analysis of variables (MANOVA), multivariate analysis of variance (MANCOVA), principal component analysis (PCA), canonical association analysis, redundancy analysis (RDA), correspondence analysis (CA), canonical correspondence analysis (CCA), multidimensional scaling, discriminant analysis, linear discriminant analysis (LDA), clustering systems, recursive adaptive blocking, vector autoregression, principal response curve analysis (PRC), etc. In an exemplary embodiment, predicting the response to minoxidil treatment may include the implementation of a neural network.

[0117] It is understood that the methods disclosed herein are implemented via a computer device or processor. For example, a computer device including a processor and a memory can communicate with a detection device (which can also have a processor and a memory). Each of these devices can have a transceiver, a transmitter, a communication bus, etc. to facilitate communication (wireless or hard-wired) between the two.

[0118] Any processor disclosed herein may be part of or in communication with a machine (e.g., a computer device, a logic device, a circuit, an operating module (hardware, software and / or firmware), etc.). A processor may be hardware (e.g., a processor, an integrated circuit, a central processing unit, a microprocessor, a core processor, a computer device, etc.), firmware, software, etc., configured to perform operations by executing instructions contained in computer program code, algorithms, program logic, control, logic, data processing program logic, artificial intelligence programming, machine learning programming, artificial neural network programming, automatic reasoning programming, etc.

[0119] Any processor disclosed herein may be an extensible processor, a parallelizable processor, a multithreaded processing processor, etc. The processor may be a computer in which processing power is selected as a function of expected network traffic (e.g., data flow). The processor may include any integrated circuit or other electronic device (or a collection of devices) capable of performing operations on at least one instruction, which may include a reduced instruction set core (RISC) processor, a complex instruction set computer (CISC) microprocessor, a microcontroller unit (MCU), a CISC-based central processing unit (CPU), a digital signal processor (DSP), a graphics processing unit (GPU), a field programmable gate array (FPGA), etc. The hardware of such a device may be integrated into a single substrate (e.g., silicon "ie"), or distributed in two or more substrates. Various functional aspects of the processor may be implemented separately as software or firmware associated with the processor.

[0120] The processor may include one or more processing or operating modules. A processing or operating module may be a software or firmware operating module configured to implement any of the functions disclosed herein. A processing or operating module may be embodied as software and stored in a memory that is operably associated with the processor. A processing module may be embodied as a web application, a desktop application, a console application, etc.

[0121] The processor may include a computer or machine readable medium, or be associated with a computer or machine readable medium. The computer or machine readable medium may include a memory. Any memory discussed herein may be a computer readable memory configured to store data. The memory may include volatile or non-volatile, transitory or non-transitory memory, and may be embodied as internal memory, active memory, cloud memory, etc. Examples of memory may include flash memory, random access memory (RAM), read-only memory (ROM), programmable read-only memory (PROM), erasable programmable read-only memory (EPROM), electronic erasable programmable read-only memory (EEPROM), flash-EPROM, compact disk (CD)-ROM, digital compact disk DVD), optical memory, optical medium, carrier wave, cassette, tape, disk storage or other magnetic storage device, or may be used to store the required information and any other medium that can be accessed by the processor.

[0122] The memory may be a non-temporary computer-readable medium. The term "computer-readable medium" (or "machine-readable medium") used herein is an extensible term that refers to any medium or any memory that participates in providing instructions to a processor for execution, or any mechanism for storing or transmitting information in a machine (e.g., computer) readable form. Such a medium may store computer-executable instructions to be executed by a processing element and / or control logic, as well as data manipulated by the processing element and / or control logic, and may take a variety of forms, including but not limited to non-volatile media, volatile media, transmission media, etc. A computer or machine-readable medium may be configured to store one or more instructions thereon. Instructions may be in the form of algorithms, program logic, etc. This enables the processor to perform any function disclosed herein.

[0123] Embodiments of the memory may include processor modules and other circuits to allow data to be transmitted to and from the memory, and the memory may include data to and from other components of the communication system. The transmission may be by hard wiring or wireless transmission. The communication system may include a transceiver, which may be used in conjunction with a switch, a receiver, a transmitter, a router, a gateway, a waveguide, etc., to facilitate communication by a communication method or protocol, for controlling and coordinating signal transmission and processing to any other component or combination of components of the communication system. Transmission may be performed via a communication link. The communication link may be electronically based, optically based, photoelectrically based, quantum based, etc. Communication may be performed via Bluetooth, near field communication, cellular communication, telemetry communication, Internet communication, etc.

[0124] The transmission of data and signals can be through a transmission medium. Transmission media can include coaxial cables, copper wires, optical fibers, etc. Transmission media can also take the form of sound waves or light waves, such as those generated during radio wave and infrared data communications, or other forms of propagated signals (such as carrier waves, digital signals, etc.).

[0125] Any processor may communicate with other processors of other devices (e.g., computing devices, computer systems, laptop computers, desktop computers, etc.). Any processor may have a transceiver or other communication device / circuitry to facilitate the transmission and reception of wireless signals. Any processor may include an application programming interface (API) as a software intermediary that allows two or more applications to talk to each other.

[0126] Another exemplary embodiment may be directed to a method for selecting a treatment for a human subject suffering from androgenetic alopecia. The method may include measuring sulfotransferase activity in a sample of the patient to generate an activity value indicative of a biochemical activation response to minoxidil (which in some embodiments may include SULT1A1 gene expression and / or SULT1A1 gene variant expression in the sample). The method may include comparing the activity value to a standardized activity value. The method may include predicting a response to minoxidil treatment based on the comparison. The method may include prescribing a minoxidil dosage amount, a minoxidil dosage frequency, and / or a minoxidil dosage routine prescription as a treatment for androgenetic alopecia.

[0127] In some embodiments, prescribing a minoxidil dosage amount, a minoxidil dosage frequency, and / or a minoxidil dosage routine can include prescribing oral minoxidil or topical minoxidil.

[0128] In some embodiments, predicting a response to minoxidil treatment can include estimating that the patient will respond well to topical minoxidil when the activity value is below a threshold normalized activity value, and estimating that the patient will respond poorly to oral minoxidil when the activity value is above the threshold normalized activity value.

[0129] In some embodiments, prescribing a treatment for androgenic alopecia can include prescribing topical minoxidil when the activity value is below a threshold normalized activity value, and not prescribing oral minoxidil when the activity value is above the threshold normalized activity value.

[0130] The foregoing is an exemplary mode of implementing the invention and is not intended to be limiting. It will be apparent to one of ordinary skill in the art that modifications may be made thereto without departing from the spirit and scope of the invention as set forth in the following claims.

Claims

1. A method for predicting a response to minoxidil, the method comprising: measuring gene, genetic and / or enzyme activity in a sample from the patient to produce an activity value indicative of a biochemical activation response to minoxidil; comparing the activity value to a standardized activity value; and The response to minoxidil treatment is predicted based on the comparison.

2. The method according to claim 1, wherein: Measurements of genetic, hereditary and / or enzyme activity include: measuring SULT1A1 gene expression, SULT1A1 gene variant expression, and / or SULT1A1 enzyme activity in a sample; measuring SLC22A9 gene expression, SLC22A9 gene variant expression, SLC22A9 transporter activity from hair cells, and / or measuring SLC22A9 transporter activity in a sample; measuring AABC3 gene expression and / or AABC3 gene variant expression in the sample; and / or Measuring blood flow in a patient.

3. The method according to claim 1, wherein: The minoxidil treatment is oral minoxidil.

4. The method according to claim 2, wherein: Predictors of response to minoxidil treatment include: When the gene, inheritance and / or enzyme activity involves SULT1A1: At activity values ​​below the threshold standardized activity value, it is estimated that the patient will respond to oral minoxidil; and At activity values ​​above the threshold standardized activity value, it is estimated that the patient will respond poorly to oral minoxidil; When SLC22A9 is involved genetically, hereditarily, and / or from hair cells SLC22A9 transporter activity: When the activity value is above the threshold standardized activity value, it is estimated that the patient will respond to oral minoxidil; and At activity values ​​below the threshold standardized activity value, it is estimated that the patient will respond poorly to oral minoxidil; and When genes and / or genetic activity involve AABC3: At activity values ​​below the threshold standardized activity value, it is estimated that the patient will respond to oral minoxidil; and At activity values ​​above the threshold standardized activity value, it is estimated that the patient will respond poorly to oral minoxidil.

5. The method according to claim 1, wherein: Measuring a patient's blood flow includes Doppler velocimetry; Predictors of response to minoxidil treatment include: When Doppler velocities are below the threshold, it is estimated that the patient will respond well to oral minoxidil; and At Doppler velocities above the threshold, it is estimated that the patient will respond poorly to oral minoxidil.

6. The method of claim 1, wherein measuring SLC22A9 transport activity from hair cells comprises using an uptake assay.

7. The method according to claim 1, wherein when the gene, heredity and / or enzyme activity involves SULT1A1: At activity values ​​below a threshold standardized activity value in the range of 0.37 to 0.4, it is estimated that the patient will respond well to oral minoxidil; and At activity values ​​above a threshold standardized activity value in the range of 0.37 to 0.4, it is estimated that the patient will respond poorly to oral minoxidil.

8. The method of claim 1, wherein: Minoxidil treatment is used to treat androgenetic alopecia.

9. The method according to claim 1, comprising: generating a plurality of activity values ​​indicative of a biochemical activation response to minoxidil; and The plurality of activity values ​​are compared to a plurality of standard activity values.

10. The method of claim 1, wherein: The response to minoxidil treatment is increased or improved hair growth or hair retention.

11. The method according to claim 1, wherein: Predicting the response to minoxidil treatment includes routine estimation of the biochemical activation response based on the minoxidil dose amount, minoxidil dose frequency, and / or minoxidil dose.

12. The method of claim 1, wherein: The normalized activity value relates to the biochemical activation response to minoxidil associated with hair growth or hair retention in an individual category.

13. The method of claim 1, wherein: The normalized activity value relates to the biochemical activation response to minoxidil associated with hair growth or hair retention, where a statistical sample of subjects shows a high or low minoxidil response to minoxidil dosage amount, minoxidil dosage frequency, and / or minoxidil dosage routine.

14. The method of claim 1, wherein: Measuring gene, genetic and / or enzyme activity in a sample from a patient includes obtaining one or more hair follicles and / or one or more scalp biopsies as a sample.

15. The method of claim 1, wherein: Genetic, genetic and / or enzymatic activity is measured in a sample from the patient before, during and / or after minoxidil treatment is administered to the patient.

16. The method of claim 1, wherein: Sulfotransferase activity is measured in samples from patients 1 to 14 days prior to administering minoxidil treatment to the patients.

17. The method of claim 1, wherein: Measuring genetic, hereditary and / or enzymatic activity in a patient's sample is performed via a detection device.

18. The method of claim 1, wherein: Measuring genetic, hereditary and / or enzymatic activity in a patient's sample is performed via a colorimetric assay device.

19. The method of claim 1, wherein: Prediction of response to minoxidil treatment involves implementation of a neural network.

20. The method of claim 1, wherein measuring the gene, genetic and / or enzyme activity in the patient's sample comprises obtaining one or more hair follicles and / or one or more scalp biopsies as samples, and measuring the gene, genetic and / or enzyme activity in the patient's sample is achieved via a detection device, the method comprising: placing one or more hair follicles or one or more scalp biopsies in a reaction mixture containing potassium phosphate buffer, magnesium chloride, adenosine 3',5'-diphosphate (PAP) or adenosine 3'-phosphate, 5'-phosphosulfate (PAPS), p-nitrophenyl sulfate, and minoxidil; mixing the reaction mixture; incubating the reaction mixture for a predetermined period of time; and Stop the reaction.

21. A method for selecting a treatment for a human subject suffering from androgenetic alopecia, the method comprising: measuring gene, genetic and / or enzyme activity in a sample from the patient to produce an activity value indicative of a biochemical activation response to minoxidil; comparing the activity value to a standardized activity value; predicting a response to minoxidil treatment based on said comparison; and Prescribing minoxidil dosage amount, minoxidil dosage frequency, and / or minoxidil dosage routine as a treatment for androgenetic alopecia.

22. The method of claim 21, wherein: Measurements of genetic, hereditary and / or enzyme activity include: measuring SULT1A1 gene expression, SULT1A1 gene variant expression, and / or SULT1A1 enzyme activity in a sample; measuring SLC22A9 gene expression, SLC22A9 gene variant expression, SLC22A9 transporter activity from hair cells, and / or SCL22A9 transporter activity in the sample; measuring AABC3 gene expression and / or AABC3 gene variant expression in the sample; and / or Measuring blood flow in a patient.

23. The method of claim 21, wherein: Prescribing a minoxidil dosage amount, a minoxidil dosage frequency, and / or a minoxidil dosage routine includes prescribing oral minoxidil.

24. The method of claim 21, wherein: Measuring a patient's blood flow includes Doppler velocimetry; Predictors of response to minoxidil treatment include: When the Doppler velocity is below the threshold, it is estimated that the patient will respond well to oral minoxidil; and At Doppler velocities above the threshold, it is estimated that the patient will respond poorly to oral minoxidil.

25. The method of claim 21, wherein: Predictors of response to minoxidil treatment include: When genes, genetics and / or enzyme activity are involved in SULT1A1: At activity values ​​below the threshold standardized activity value, it is estimated that the patient will respond to oral minoxidil, and At activity values ​​above the threshold standardized activity value, it is estimated that the patient will respond poorly to oral minoxidil; When SLC22A9 is involved genetically, hereditarily, and / or from hair cells SLC22A9 transporter activity: At activity values ​​above the threshold standardized activity value, it is estimated that the patient will respond to oral minoxidil, and At activity values ​​below the threshold standardized activity value, it is estimated that the patient will respond poorly to oral minoxidil; and When genes and / or genetic activity involve AABC3: At activity values ​​below the threshold standardized activity value, it is estimated that the patient will respond to oral minoxidil, and At activity values ​​above the threshold standardized activity value, it is estimated that the patient will respond poorly to oral minoxidil.

26. The method of claim 21, wherein when genes, heredity and / or enzyme activity are involved in SULT1A1: At activity values ​​below a threshold standardized activity value in the range of 0.37 to 0.4, it is estimated that the patient will respond well to oral minoxidil; and At activity values ​​above a threshold standardized activity value in the range of 0.37 to 0.4, it is estimated that the patient will respond poorly to oral minoxidil.

27. The method of claim 21, wherein measuring SLC22A9 transport activity from hair cells comprises using an uptake assay.

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