Systems and methods for predicting response to oral minoxidil for treatment of androgenetic alopecia

Abstract

To provide scientific diagnostic tests available for alopecia, and methods to predict treatment response.SOLUTION: Methods, processes, systems, and apparatuses are disclosed for predicting minoxidil response in the treatment of androgenetic alopecia, and prescribing a minoxidil dosage amount, minoxidil dosage frequency, and / or minoxidil dosage routine based on the same.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This patent application is related to and claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 512,137, filed July 6, 2023, the entire contents of which are incorporated by reference.

[0002] The invention described herein relates to systems and methods for predicting response to oral minoxidil treatment (minoxidil therapy) for the treatment of androgenetic alopecia. [Background technology]

[0003] Hair loss is associated with various psychological and social implications.Before starting any treatment, it is advantageous to predict the course, severity and treatment options of the disease.In the field of hair loss, there are currently few scientific diagnostic tests available, and there are few methods to predict treatment response.

[0004] Additionally, the hair loss industry is flooded with numerous products that claim to grow, improve, and replace hair. Unfortunately, few treatments have been scientifically proven to be effective, and the few that have undergone clinical trials often do not work equally for all patients.

[0005] Androgenetic alopecia has been successfully treated in men with the U.S. Food and Drug Administration ("FDA") approved drug minoxidil (marketed as Rogaine™ or Regaine™). Minoxidil has also been approved by the FDA for the treatment of hair loss in women, but for most women, minoxidil is only moderately successful in preserving existing hair. Some men for whom minoxidil is less effective have been successfully treated with finasteride, but the same cannot be said for women for whom minoxidil is ineffective. Previous studies have failed to show the effectiveness of finasteride in treating androgenetic alopecia in women.

[0006] There is a significant difference between male and female androgenetic alopecia. Apart from different hair loss patterns, male and female alopecia follow different mechanisms. In men, alopecia is associated with the normal high androgen levels of men, combined with the underlying sensitivity of hair roots to androgens.However, women have approximately 10 times lower androgen levels than men, and the absolute amount of androgens is not a significant factor compared to the increased sensitivity of hair roots to androgens.

[0007] Among different individuals, whether male or female, there is a wide variability in the response of different people to different hair loss treatments.This variability is presumed to be the result of genetic factors that contribute to variable enzyme activity in hair follicles, making it difficult to achieve a one-size-fits-all approach.Therefore, it would be advantageous to have an effective diagnostic and treatment method that can select and treat patients based on criteria such as enzyme activity, which identifies some people as likely to benefit from treatment with minoxidil and other drugs, while identifying other individuals for whom treatment is unlikely to be effective.Previous methods for predicting response to minoxidil are described in U.S. Patent No. 8,691,518.However, there remains a need to predict response to oral vs. topical forms of minoxidil. Summary of the Invention

[0008] The invention described herein relates to a system and method 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 colorimetric assay.Various embodiments are possible, some of which are exemplified herein.In particular, the variation of hair follicle minoxidil sulfotransferase activity can be used to predict the effectiveness of minoxidil in the treatment of androgenetic alopecia.

[0009] In one aspect of the present disclosure, a method for selecting a treatment for a subject suffering from androgenetic alopecia is provided, comprising obtaining one or more hair follicle or scalp biopsy samples from the subject, performing an assay to measure minoxidil sulfotransferase activity in the samples, thereby generating an activity value indicative of the minoxidil sulfotransferase activity level in the samples, and comparing the activity value with one or more standard activity values, each standard activity value representing a high or low expected minoxidil response to hair regrowth or retention for a class of patients including the subject, thereby providing an indication of the high or low expected minoxidil response to hair regrowth or retention of the subject at a particular dose of minoxidil, and presenting the indication to the subject. Optionally, the indication of the high or low expected minoxidil response to hair regrowth or retention is used to select a treatment with oral or topical minoxidil.

[0010] In another aspect, components of matter for conducting an assay are provided that include 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.

[0011] In another aspect, a kit is provided that includes a transparent container having a lid containing the above-described components for conducting an assay; a buffer container containing about 0.20 M to about 0.30 M Tris-HCl, pH 8.7; and a means for mixing the contents of the buffer container with the contents of the device.

[0012] As described herein, an embodiment may relate to a method of 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 minoxidil sulfotransferase activity level in the sample. In some embodiments, placing the sample in a reaction mixture may include the use of an indicator dye and minoxidil. During the assay, the indicator dye may undergo a color change that correlates with the amount of minoxidil sulfotransferase activity level in the sample. The activity value may correlate with the color change. The method may include comparing the activity value to one or more standard activity values. Each standard activity value can represent a high or low expected minoxidil response to hair regrowth or retention for a class of patients that includes the subject, thereby providing an index of high or low expected minoxidil response to hair regrowth or retention for the subject at a particular dose of minoxidil. The method can include presenting the index to a human subject.

[0013] In some embodiments, the indication may be a high predicted minoxidil response for hair regrowth or retention, and the particular dosage of minoxidil may be selected from the group consisting of 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.

[0014] In some embodiments, the assay can include placing the sample in a reaction mixture containing about 50 mM potassium phosphate buffer having a pH of about 6.5 to 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 of time, and stopping the reaction.

[0015] In some embodiments, the potassium phosphate buffer can have a pH of about 8.0.

[0016] 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 analyte and improve the sensitivity of the assay.

[0017] In some embodiments, the reaction mixture can be incubated at about 37° C. for about 30 minutes to about 24 hours.

[0018] In some embodiments, the sample in the reaction mixture can be incubated at room temperature.

[0019] In some embodiments, the reaction mixture can be incubated above room temperature to increase dye turnover and signal intensity of the colorimetric assay.

[0020] In some embodiments, the reaction mixture can be packaged in a capsule and dissolved in solution along with the sample.

[0021] In some aspects, the one or more standard values ​​can be one or more minoxidil sulfotransferase activity levels at which a statistical sample of other subjects exhibits a higher or lower minoxidil response to hair regrowth or retention at a particular dosage of minoxidil.

[0022] In some aspects, the presenting step can include transmitting an electronic signal.

[0023] In some embodiments, the indicator dye can be p-nitrophenyl sulfate.

[0024] In some embodiments, the colorimetric assay can use 2-naphthol as a substrate to improve the sensitivity or specificity of the assay.

[0025] In some embodiments, the sample may consist of a single hair containing one hair follicle plucked from a human subject.

[0026] In some embodiments, the reaction time of the assay can be inversely correlated with the number of reacting hair follicles.

[0027] In some embodiments, human subjects with high minoxidil sulfotransferase activity may be prescribed lower doses of minoxidil and / or reduced frequency of minoxidil application.

[0028] In some embodiments, human subjects with low minoxidil sulfotransferase activity may be prescribed higher doses of minoxidil and / or increased frequency of minoxidil application.

[0029] In some embodiments, a stabilized form of minoxidil sulfate in the form of a cream, solution and / or gel can be prescribed to a human subject with low minoxidil sulfotransferase activity.

[0030] In some embodiments, minoxidil sulfate may be stabilized in liposomes or microencapsulation.

[0031] In some embodiments, the assay can include positive (reference) and negative (blank) controls for comparison to the sample.

[0032] In some embodiments, the color change may be visually discernible, hi some embodiments, the assay may be performed in a transparent container.

[0033] In some embodiments, generating an activity value can be done by comparing the distinguishable color after the color change to a reference color card.

[0034] In some embodiments, the colorimetric assay can be performed in a transparent container and the generation of activity values ​​is performed by measuring absorbance at about 405 nm in a spectrophotometer.

[0035] Another exemplary embodiment may relate to a method of predicting a response to minoxidil. The method may include measuring gene, genetic, and / or enzymatic activity in a patient sample to generate an activity value indicative of a biochemical activation response to minoxidil. The method may include comparing the activity value to a standard activity value. The method may include predicting a response to treatment with minoxidil based on the comparison.

[0036] In some embodiments, measuring gene or enzyme activity can include measuring SULT1A1 gene expression, SULT1A1 gene variant expression, and / or SULT1A1 enzyme activity in the sample; measuring SLC22A9 gene expression, SLC22A9 gene variant expression, SLC22A9 transporter activity from hair cells in the sample, and / or SLC22A9 transporter activity from hair cells in the sample; measuring AABC3 gene expression and / or AABC3 gene variant expression in the sample; and / or measuring blood flow in the patient (e.g., at the patient's scalp).

[0037] In some embodiments, SLC22A9 transport activity from hair cells can be measured using standard substrate uptake assays with known substrates (eg, fluorescent substrates, radioactive nuclear substrates, etc.).

[0038] In some embodiments, the minoxidil treatment can be oral minoxidil treatment.

[0039] In some embodiments, predicting the response to treatment with minoxidil comprises: if the gene activity, genetic activity, and / or enzymatic activity is associated with SULT1A1, then predicting that the patient will respond to oral minoxidil treatment if the activity value is below the threshold standard activity value and predicting that the patient will not respond to oral minoxidil treatment if the activity value is above the threshold standard activity value; if the gene activity, genetic activity and / or SLC22A9 transporter activity is associated with SLC22A9, predicting that the patient will respond to oral minoxidil treatment if the activity value is higher than the threshold standard activity value and predicting that the patient will not respond adequately to oral minoxidil treatment if the activity value is lower than the threshold standard activity value; If the gene activity and / or genetic activity is associated with AABC3, predicting that the patient will respond to oral minoxidil treatment if the activity value is below the threshold standard activity value and predicting that the patient will not respond adequately to oral minoxidil treatment if the activity value is above the threshold standard activity value. may include.

[0040] In some embodiments, measuring blood flow in the patient (e.g., the patient's scalp) can include Doppler velocity measurements. Predicting the response to treatment with minoxidil can include presuming that the patient will respond well to oral minoxidil treatment if the Doppler velocity is below a threshold value, and presuming that the patient will not respond well to oral minoxidil treatment if the Doppler velocity is above a threshold value.

[0041] In some embodiments, where the gene activity, genetic activity, and / or enzymatic activity is for SULT1A1, a patient is predicted to respond well to oral minoxidil treatment if the activity value is lower than a threshold standard activity value, which is within the range of 0.37 to 0.4, and a patient is predicted to respond poorly to oral minoxidil treatment if the activity value is higher than a threshold standard activity value, which is within the range of 0.37 to 0.4.

[0042] In some embodiments, the minoxidil treatment can be a treatment for androgenetic alopecia.

[0043] In some aspects, the method can 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.

[0044] In some aspects, the response to treatment with minoxidil can be an increase or improvement in hair growth or hair retention.

[0045] In some aspects, predicting the response to treatment with minoxidil can include estimating a biochemical activation response based on a minoxidil dosage, a minoxidil dosage frequency, and / or a minoxidil dosage routine.

[0046] In some aspects, the standard activity value may relate to a biochemical activation response to minoxidil that is associated with hair growth or hair retention for a class of individuals.

[0047] In some aspects, the standard activity value can relate to a biochemical activation response to minoxidil associated with hair growth or hair retention, where a statistical sample of subjects exhibits a high or low minoxidil response for a minoxidil dosage, a minoxidil dosing frequency, and / or a minoxidil dosing routine.

[0048] In some embodiments, measuring gene activity, genetic activity, and / or enzyme activity in a patient sample may include obtaining one or more hair follicle and / or one or more scalp biopsies as the sample.

[0049] In some embodiments, measuring gene activity, genetic activity, and / or enzyme activity in a patient sample can be performed before, during, and / or after the patient is treated with minoxidil.

[0050] In some embodiments, measuring gene activity, genetic activity, and / or enzyme activity in a patient sample can be performed 1-14 days before the patient is treated with minoxidil.

[0051] In some embodiments, measuring gene activity, genetic activity, and / or enzymatic activity in a patient sample can be performed via an assay device.

[0052] In some embodiments, measuring gene activity, genetic activity, and / or enzyme activity in a patient sample can be performed via a colorimetric assay device.

[0053] In some aspects, predicting the response to treatment with minoxidil can include implementing a neural network.

[0054] In some embodiments, measuring gene activity, genetic activity, and / or enzymatic activity in a patient sample can include obtaining one or more hair follicles and / or one or more scalp biopsies as a sample, and measuring gene activity, genetic activity, and / or enzymatic activity in the patient sample is performed via an assay device, and the method includes 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 length of time, and stopping the reaction.

[0055] Another exemplary embodiment may be a method for selecting a treatment for a human subject suffering from androgenetic alopecia. The method may include measuring gene activity, genetic activity, and / or enzyme activity in a patient sample to generate an activity value indicating a biochemical activation response to minoxidil. The method may include comparing the activity value with a standard activity value. The method may include predicting a response to treatment with minoxidil based on the comparison. The method may include prescribing a minoxidil dosage, a minoxidil administration frequency, and / or a minoxidil administration routine as an androgenetic alopecia treatment.

[0056] In some embodiments, measuring gene activity, genetic activity, and / or enzyme activity can include measuring SULT1A1 gene expression, SULT1A1 gene variant expression, and / or SULT1A1 enzyme activity in the sample; measuring SLC22A9 gene expression, SCL22A9 gene variant expression, SLC22A9 activity from hair follicles in the sample, and / or SLC transporter activity; measuring AABC3 gene expression and / or AABC3 gene variant expression in the sample; and / or measuring blood flow in the patient.

[0057] In some embodiments, prescribing a minoxidil dosage, a minoxidil dosage frequency, and / or a minoxidil dosage routine can include prescribing oral minoxidil.

[0058] In some embodiments, measuring blood flow in the patient (e.g., the patient's scalp) can include Doppler velocity measurements. Predicting the response to treatment with minoxidil can include presuming that the patient will respond well to oral minoxidil treatment if the Doppler velocity is below a threshold value, and presuming that the patient will not respond well to oral minoxidil treatment if the Doppler velocity is above a threshold value.

[0059] In some embodiments, predicting the response to treatment with minoxidil comprises: if the gene activity, genetic activity and / or enzymatic activity is associated with SULT1A1, predicting that the patient will respond to oral minoxidil treatment if the activity value is below the threshold standard activity value and predicting that the patient will not respond adequately to oral minoxidil treatment if the activity value is above the threshold standard activity value; if the gene activity, genetic activity and / or SLC22A9 transporter activity from the hair cells is associated with SLC22A9, predicting that the patient will respond to oral minoxidil treatment if the activity value is higher than the threshold standard activity value and predicting that the patient will not respond adequately to oral minoxidil treatment if the activity value is lower than the threshold standard activity value; If the gene activity and / or genetic activity is associated with AABC3, predicting that the patient will respond to oral minoxidil treatment if the activity value is below the threshold standard activity value and predicting that the patient will not respond adequately to oral minoxidil treatment if the activity value is above the threshold standard activity value. may include.

[0060] In some embodiments, where the gene activity, genetic activity, and / or enzymatic activity is for SULT1A1, a patient is predicted to respond well to oral minoxidil treatment if the activity value is lower than a threshold standard activity value, which is within the range of 0.37 to 0.4, and a patient is predicted to respond poorly to oral minoxidil treatment if the activity value is higher than a threshold standard activity value, which is within the range of 0.37 to 0.4.

[0061] The accompanying drawings incorporated herein illustrate one or more exemplary aspects of the inventions disclosed herein and, together with the detailed description, serve to explain the principles and exemplary implementations of these inventions. Those skilled in the art will understand that the drawings are merely illustrative and that what is shown therein may be adapted based on the text of the specification or common knowledge in the field.

[0062] In the drawings, like reference numbers refer to like references throughout the specification. [Brief description of the drawings]

[0063] [Figure 1] 1 is a flowchart illustrating a method of analyzing one or more hair follicles and providing results.

[0064] [Diagram 2] FIG. 1 shows an example of a computerized system for performing or analyzing an assay to test hair follicles and provide results.

[0065] [Diagram 3] FIG. 1 is a flow diagram of minoxidil sulfonation. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0066] Various exemplary aspects of the invention are described herein in the context of treating androgenetic alopecia.

[0067] The description herein is provided in the context of treating androgenetic alopecia.Those skilled in the art will understand that the following detailed description is merely illustrative and is not intended to be limiting in any way.Other aspects will be readily suggested to those skilled in the art who have the benefit of this disclosure.Now, detailed reference will be made to the embodiments shown in the accompanying drawings.The same reference numerals are used throughout the drawings and the following detailed description to refer to the same or similar parts.

[0068] For clarity, not all of the routine features of the implementations described herein are shown and described. Of course, it will be understood that the development of any such actual implementation will require numerous implementation-specific decisions to be made in order to achieve the developer's particular goals, such as adhering to application and business-related constraints, and that these particular goals will vary from implementation to implementation and from developer to developer. Moreover, it will be understood that such a development effort may be complex and time-consuming, but will nevertheless be a routine undertaking of engineering for those of ordinary skill in the art having the benefit of this disclosure.

[0069] Androgenetic alopecia is extremely common, affecting approximately 60% of men and over 50% of women by age 60. Currently, there are two FDA-approved drugs for the treatment of androgenetic alopecia: finasteride and minoxidil. However, finasteride therapy, which has been successful in re-growth and maintenance of hair in men, has failed to show significant improvement in women. Thus, minoxidil is currently the only FDA-approved drug for female hair loss. Furthermore, for treatment with minoxidil to be effective, it often must be used for a long period of time without knowing whether it is effective or not. One objective of the present invention is to screen patients before treatment begins and / or during treatment to determine which patients respond best to treatment with minoxidil, and further to determine which form of minoxidil (e.g., topical or oral) to which the patient responds best, thereby providing an individualized and effective treatment for hair loss.

[0070] The present invention is based in part on the discovery that minoxidil requires biochemical activation by minoxidil sulfotransferase, i.e. SULT1A1, to form the active metabolite minoxidil sulfate.The exact mechanism of action of minoxidil-based treatment of androgenetic alopecia is not fully understood.However, in vitro studies have demonstrated that minoxidil sulfate is the active metabolite of minoxidil.The response to minoxidil for the treatment of androgenetic alopecia is associated with differences in scalp sulfotransferase activity.Therefore, it is generally accepted that subjects with high levels of minoxidil sulfotransferase activity are more likely to produce more minoxidil sulfate and therefore have a good response to minoxidil for the treatment of androgenetic alopecia.On the other hand, subjects with low levels of minoxidil sulfotransferase activity are less likely to produce minoxidil sulfate and have a poor response to minoxidil for the treatment of androgenetic alopecia.

[0071] Clinical trials with minoxidil for the treatment of androgenetic alopecia have shown statistically significant results for hair maintenance and growth.Several studies have demonstrated that the level of minoxidil sulfotransferase activity is significantly higher in patients who respond to minoxidil for the treatment of androgenetic alopecia.As described herein, the assessment of hair regrowth is based on one or more of the following parameters: patient self-assessment, physician assessment using standard scales, global photography assessment, hair diameter measurement, hair average length measurement, hair average diameter measurement, and hair weight measurement.The present invention provides a method of using biochemical variations in minoxidil sulfotransferase activity as a drug response marker for the treatment of androgenetic alopecia with oral and / or topical minoxidil.Based on minoxidil sulfotransferase activity level, the method disclosed herein allows physicians or patients to select the appropriate treatment and its dosage for the treatment of androgenetic alopecia.

[0072] According to one approach described herein, hair follicle samples can be obtained from patients.Preferably, at least two hair follicles can be obtained, so that if only one is analyzed, there is at least one back-up, if necessary.In one embodiment, hair follicle samples are taken before the start of treatment with minoxidil.In another embodiment, hair follicle samples are taken after the start of treatment with minoxidil.

[0073] A patient's hair follicle sample can be subjected to a colorimetric assay to determine the level of minoxidil sulfotransferase activity. A patient's hair follicle sample (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.

[0074] In one embodiment, the reaction can be carried out in a transparent container having a lid or other opening into which the hair follicle sample can be inserted. In one non-limiting example, the total volume of liquid in the assay container can be about 0.2 ml.

[0075] It is understood that as part of the above reaction, in the presence of minoxidil sulfotransferase activity, p-nitrophenyl sulfate is converted to colorimetric p-nitrophenolate.

[0076] The reactants may be mixed and then incubated at 37°C for about 4 to 16 hours, depending on the number of hair follicles used in the assay. Mixing may be by any mixing means known in the art, including shaking the container. For more hair follicles, shorter incubation times are required. In one embodiment, an assay using one hair follicle may be incubated for about 16 hours. In another embodiment, an assay using two hair follicles may be incubated for about 4 hours.

[0077] After incubation of the samples, the reaction may be stopped by the addition of about 1 / 10 volume of about 0.25 M Tris-HCl buffer (pH 8.7) and mixed. The pH may vary between 8.5 and 9.0 in one embodiment. The basic buffer may be provided as a separate container for pouring into the assay reaction vessel, particularly if the assay is performed or sold as part of a kit. In another embodiment, the basic buffer may be provided in a pre-filled syringe to be injected into the main reaction vessel at the appropriate time by manually pressing a plunger or by some automated or computerized control.

[0078] The absorbance at about 405 nm can then be read on a spectrophotometer or compared to a reference color card having a range of intensities corresponding to minoxidil sulfotransferase activity. Patients with relatively high levels of sulfotransferase activity will have relatively strong colorimetric readings, resulting in relatively significant color changes. In comparison, patients with relatively low levels of sulfotransferase activity will have relatively weak colorimetric readings, correspondingly with relatively minimal color changes. Patients with a strong colorimetric assay response are expected to respond to minoxidil for hair regrowth or retention. On the other hand, patients with a weak colorimetric assay response are expected to respond poorly to minoxidil.

[0079] In yet another embodiment, the results of the hair follicle colorimetric assay of the patient are used to determine the optimal treatment plan. This includes determining the method of delivery of minoxidil (oral vs. topical); or modifying the concentration and / or frequency of treatment with minoxidil to match the patient's minoxidil sulfotransferase activity. Furthermore, if the patient is unlikely to respond to minoxidil, finasteride may be recommended as an alternative to minoxidil.

[0080] Referring to FIG. 1, the method 100 described herein includes, at 102, collection of a hair follicle sample from a subject. Collection may occur before and / or after the initiation of treatment with minoxidil. The hair follicle sample may then be coded with a unique identifier at 104, 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 a colorimetric assay as described herein. The results of the analysis may then be provided to the subject or the subject's caregiver at 108. The results of the analysis, each associated with its unique identifier, may be transmitted to a computer system, which may include, for example, a web-based server accessible with appropriate authentication by the subject or caregiver using the unique identifier. In addition to providing an indication of the likelihood that the patient will respond to 2%, 5% or more of minoxidil for the treatment of androgenetic alopecia, the results may also include a prediction of the required dosage and daily treatment frequency by comparing the patient's minoxidil sulfotransferase activity level to a reference database. The results also provide an indication of the likelihood that a patient will respond to oral or topical application of minoxidil for the treatment of androgenetic alopecia.

[0081] FIG. 2 shows a schematic of a system 200 for carrying out the above procedures. A hair follicle sample 202 from a subject is sent to a laboratory 204. The sample is then analyzed by one or more of the procedures described above. The results of the analysis are compared to a database to generate an indication of the likelihood that the patient will respond to oral or topical application of minoxidil for the treatment of androgenetic alopecia, for example. The database is dynamic in nature and may be continuously updated for statistical adaptation based on past minoxidil treatments and responses thereto, so that the database can adapt or learn from patient pools and treatments over time, thus becoming a better predictor of the likelihood of responders to drug treatment. The database, or other entities or circuits or modules capable of the adaptation methods described herein, may reside within a computer system 206 or may reside separately therefrom. The results of the comparison and analysis may be transferred electronically, for example via a network such as the Internet 210, to a patient or caregiver's computer system 208. Alternatively or additionally, the results of the comparison and analysis may be stored on the server 212 for remote access by the subject or caregiver after appropriate authentication, which may require reference to a unique identifier to protect privacy.

[0082] Table 1, consisting of Tables 1-1 and 1-2 below, shows the results of testing patients' responsiveness to minoxidil. In one embodiment, the test is performed by placing hair follicles in the assay. The hair follicles can be taken before treatment with minoxidil or after the start of treatment with minoxidil. The hair follicles are placed in a solution containing minoxidil. The assay is then performed as described above and examined to determine whether there is a SULT1A1 response. The results are then used as a predictor of patients who will respond well to minoxidil and respond well to oral minoxidil treatment compared to topical application of minoxidil. Table 1 shows the response raw data values ​​for the described tests. The first column is the optical density obtained from the colorimetric test. The second column shows the response. This test shows that the method used to predict oral (tablet) response cannot be used to predict response to topical minoxidil.

[0083] This study shows that low sulfotransferase activity is significantly associated with response to topical minoxidil.Therefore, low SULT1A1 expression is a predictor that patients will respond well to topical minoxidil.Conversely, high sulfotransferase activity is associated with a low likelihood of responding to oral minoxidil treatment for androgenetic alopecia.Therefore, high SULT1A1 expression is a predictor that patients will not respond well to topical minoxidil. [Table 1-1] [Table 1-2]

[0084] The study shows a correlation between high SULT1A1 expression in hair follicles when exposed to minoxidil and a lower likelihood of having a good response to oral minoxidil treatment, likely due to asphyxiation in the liver and dissolution of minoxidil in tissues when the oral form is used.

[0085] Additionally or alternatively, the test can be used to examine genetic variations in the SULT1A1 gene, whereby variants that predispose to low SULT1A1 expression can be used to predict response to a route of treatment with minoxidil, a dose of treatment with minoxidil, and a frequency of treatment, or a combination thereof.

[0086] It may also be possible to use neural network to implement the system and method to predict the likelihood of a patient responding to minoxidil for the treatment of androgenetic alopecia based on the patient's minoxidil sulfotransferase activity profile. According to such an approach, it can include: (a) constructing an N-layer neural network; and (b) using a data set of the patient's outcome to the treatment with minoxidil for androgenetic alopecia together with the patient's minoxidil sulfotransferase activity profile to predict the likelihood of response to drug treatment; (c) obtaining a hair follicle sample from the subject; (d) generating a minoxidil sulfotransferase activity profile from the sample, the profile being a function of values ​​related to a predetermined 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 drug treatment at single or multiple doses; and (g) providing the patient with drug treatment at recommended doses.

[0087] As can be understood from the present disclosure, an embodiment can relate to a method for predicting a response to minoxidil. The method can include measuring sulfotransferase activity in a patient sample to generate an activity value indicative of a biochemical activation response to minoxidil. Measuring sulfotransferase activity can optionally include measuring SULT1A1 gene expression and / or SULT1A1 gene variant expression in the sample. Measuring sulfotransferase activity in the patient sample can include obtaining one or more hair follicles and / or one or more scalp biopsies as the sample. For example, the sample can be subjected to a colorimetric assay to determine the level of sulfotransferase activity. For example, measuring sulfotransferase activity in the patient sample can include obtaining one or more hair follicles and / or one or more scalp biopsies as the sample, and measuring sulfotransferase activity in the patient sample is performed via an assay device, and the method includes: 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; ii. mixing the reaction mixture and incubating the reaction mixture for a predetermined length of time; iii. Stopping the reaction; Includes.

[0088] As a non-limiting example, a patient's hair follicle sample (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.

[0089] It is understood that as part of the above reaction, in the presence of minoxidil sulfotransferase activity, p-nitrophenyl sulfate is converted to colorimetric p-nitrophenolate. The absorbance at about 405 nm can then be read on a spectrophotometer or compared to a reference color card having a range of intensities corresponding to minoxidil sulfotransferase activity. Patients with relatively high levels of sulfotransferase activity will have relatively strong colorimetric readings, resulting in a relatively significant color change. In comparison, patients with relatively low levels of sulfotransferase activity will have relatively weak colorimetric readings, correspondingly with relatively minimal color change. 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, and a very strong reading (or strong intensity) can be assigned a sensitivity value of 1. The reading gradation can be assigned a value between 0 and 1. The use of a scale of 0 to 1 is for illustrative purposes.

[0090] Measuring sulfotransferase activity in a patient sample can be performed before (e.g., 1-14 days before), during, and / or after the patient is treated with minoxidil. Thus, the methods disclosed herein are not limited to measuring sulfotransferase activity during or after treatment with minoxidil.

[0091] The method may include comparing the activity value to a standard activity value. The standard activity value may be determined based on empirical data obtained from a plurality of subjects treated with minoxidil and their measured responses. The comparison may be performed, for example, by comparing the activity value to a look-up table that includes a plurality of standard activity values. A prediction of the response to treatment with minoxidil may be performed based on the comparison.

[0092] In some embodiments, the treatment with minoxidil can be the treatment of androgenetic alopecia.The response to the treatment with minoxidil can be an increase or improvement in hair growth or hair retention.Predicting the response to the treatment with minoxidil can include predicting the response based on the minoxidil dosage, the minoxidil dosage frequency, and / or the minoxidil dosage routine.

[0093] As described herein, the minoxidil treatment can be oral minoxidil treatment or topical minoxidil treatment. 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 not respond well to topical minoxidil treatment. Thus, predicting the response to minoxidil treatment can include predicting that a patient will respond well to oral minoxidil treatment if the activity value is lower than a threshold standard activity value, and predicting that a patient will not respond well to oral minoxidil treatment if the activity value is higher than a threshold standard activity value. The threshold value depends on the empirical data collected, the class of individuals (e.g., male, female, race, type of alopecia, etc.), how the data is trained (if data is trained), etc. It is understood that the standard activity value may be related to the biochemical activation response to minoxidil associated with hair growth or hair retention of one or more classes of individuals. In some cases, this may be related to gene expression and / or SULT1A1 gene variant expression associated with hair growth or hair retention of one or more classes of individuals. Thus, the comparison may take into account the class of individuals from which the patient from whom the sample is taken is included. The patient may be classified into one or more classes of individuals. Some embodiments may include generating a plurality of activity values ​​(which in some embodiments may represent gene expression and / or SULT1A1 gene variant expression in the sample) indicative of the biochemical activation response to minoxidil, and comparing the plurality of activity values ​​to a plurality of standard activity values. In an exemplary embodiment, the standard activity value may be related to the biochemical activation response to minoxidil associated with hair growth or hair retention, where a statistical sample of subjects shows high or low minoxidil response for a minoxidil dosage, a minoxidil dosing frequency, and / or a minoxidil dosing routine.

[0094] In some embodiments, genetic testing of SLC family genes (e.g., SLC22A9 gene) can be used to predict response to treatment with minoxidil. Genetic testing of one or more genes of the SLC family can generate a result predicting low SLC activity or expression. For example, predicting low activity or expression of one or more genes of the SLC family in a patient can be indicative of low response to oral minoxidil or of being responsive to low oral minoxidil treatment. Predicting high activity or expression of one or more genes of the SLC family in a patient can be indicative of high response to oral minoxidil treatment or of high response to oral minoxidil treatment.

[0095] In some embodiments, genetic testing of AABC family genes (e.g., AABC3 gene) can be used to predict response to treatment with minoxidil. Genetic testing of one or more genes of the AABC family can generate results predictive of high AABC activity or expression. For example, predicting high activity or expression of one or more genes of the AABC family in a patient can be indicative of a low minoxidil response or a low response to minoxidil treatment. Predicting low activity or expression of one or more genes of the AABC family in a patient can be indicative of a high response to minoxidil treatment or a high response to oral minoxidil treatment.

[0096] It is understood that gene or genetic activity or expression can include activity or expression of protein, mRNA, DNA, and the like.

[0097] In some embodiments, the blood flow of the patient's skin (e.g., scalp) can be detected by Doppler velocimetry (LDV), photopulse plethysmography, near-infrared imaging, thermal imaging, optical coherence tomography, orthogonal polarized spectral imaging, fluorescence imaging, laser Doppler imaging, microscopy, spatial frequency domain imaging, photoacoustic detection, spectral imaging, hyperspectral imaging, and electromagnetic induction. Surrogate 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 for the treatment of alopecia. Details of the relationship between blood flow and the effectiveness of minoxidil can be seen from International Publication No. WO2017007921, which is incorporated herein by reference in its entirety. In embodiments using Doppler technology, a lower Doppler velocity can be an indicator that there is a high oral minoxidil response and / or a low local response to minoxidil.

[0098] example Data Overview A total of 123 subjects were recruited. Overall, 85% of subjects with an OD<0.37 responded to oral minoxidil (5 mg for men and 1.25 mg for women). Overall, 43% of subjects with an OD>0.37 responded to oral minoxidil (5 mg for men and 1.25 mg for women). This was statistically significant p=0.0088 (Fisher's exact test). In this cohort, oral minoxidil only worked in 42% of women and 73% of men.

[0099] Consideration This study supports the use of assays (e.g., mediator release test (MRT) assay) to distinguish between responders and non-responders to oral minoxidil. However, it was discovered that oral minoxidil acts in the opposite way to topical minoxidil for the treatment of androgenetic alopecia; that is, lower SULT1A1 enzyme activity in hair follicles predicts oral minoxidil response. This is an important and unexpected finding, since it means that oral minoxidil is sulfonated in the liver, but the response is determined by the influx transporter SLC22A9 in the hair follicle. Low or high activity of SULT1A1 in hair follicles is an indirect marker of transport expression. Patients with high SULT1A1 expression in hair follicles have corresponding high ABCC3 efflux transporter expression and low SLC22A9 influx transporter expression. Thus, they respond less well to oral minoxidil. The opposite is also true for patients with low SULT1A1 expression in hair follicles (see Figure 3).

[0100] Classification models / techniques, artificial intelligence, and the like can be used to predict response to treatment with minoxidil. For example, empirical data of standard activity values ​​can be a trained data set stored in a data store (e.g., a database). A classification model can be implemented on a processor (e.g., a computing device) to compare activity values ​​to the standard activity values ​​and / or to make predictions or inferences regarding treatment response with minoxidil. In developing a standard data set, activity data can be obtained from one or more individuals to generate a robust data set, and models can be used to determine trends, predict response status, enable the use of multivariate analysis of conditions and factors that cause or are associated with response (e.g., race, age, sex, type of alopecia, minoxidil dosage, minoxidil dosing frequency, minoxidil dosing routine, etc.). For example, multivariate modeling techniques can be used to determine which conditions or factors statistically contribute to response, changes in response, and the like. Multivariate modeling techniques can include one or more of 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 variance (MANOVA), multivariate analysis of covariance (MANCOVA), principal component analysis (PCA), canonical correlation analysis, redundancy analysis (RDA), correspondence analysis (CA), canonical correspondence analysis (CCA), multidimensional scaling, discriminant analysis, linear discriminant analysis (LDA), clustering systems, recursive adaptive partitioning, vector autoregression, principal response curve analysis (PRC), etc. In an exemplary embodiment, predicting the response to treatment with minoxidil can include the implementation of a neural network.

[0101] As can be appreciated, the implementation of the methods disclosed herein is performed via a computing device or processor. For example, a computing device including a processor and memory can be in communication with an assay device (which can also have a processor and memory). Each of these devices can have a transceiver, transmitter, communication bus, etc. to facilitate communication (wireless or wired) between the two.

[0102] Any of the processors disclosed herein may be part of or in communication with a machine (e.g., a computing device, a logic device, a circuit, an operational 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 computing device, etc.), firmware, software, etc. configured to perform operations by execution of instructions embodied in computer program code, an algorithm, a program logic, control, logic, data processing program logic, artificial intelligence programming, machine learning programming, artificial neural network programming, automated inference programming, etc.

[0103] Any of the processors disclosed herein may be scalable processors, parallelizable processors, multi-threaded processors, etc. A processor may be a computer whose processing power is selected according to expected network traffic (e.g., data flow). A processor may include any integrated circuit or other electronic device (or collection of devices) capable of performing operations on at least one instruction, which may include reduced instruction set core (RISC) processors, complex instruction set computer (CISC) microprocessors, microcontroller units (MCUs), CISC-based central processing units (CPUs), digital signal processors (DSPs), graphic processing units (GPUs), field programmable gate arrays (FPGAs), etc. The hardware of such devices may be integrated on a single substrate (e.g., silicon "ie") or distributed among two or more substrates. Various functional aspects of the processor may be implemented solely as software or firmware associated with the processor.

[0104] The processor may include one or more processing or operation modules. The processing or operation modules may be software or firmware operation modules configured to perform any of the functions disclosed herein. The processing or operation modules may be embodied as software and stored in a memory, the memory being operatively associated with the processor. The processing modules may be embodied as a web application, a desktop application, a console application, etc.

[0105] The processor may include or be associated with a computer or machine-readable medium. The computer or machine-readable medium may include a memory. Any of the memories discussed herein may be computer-readable memories configured to store data. The memory may include volatile or non-volatile, temporary or non-transient memory, and may be embodied as in-memory, active memory, cloud memory, and the like. 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), electronically erasable programmable read-only memory (EEPROM), FLASH-EPROM, compact disc (CD)-ROM, digital optical disc (DVD), optical storage device, optical medium, carrier wave, magnetic cassette, magnetic tape, magnetic disk storage device or other magnetic storage device, or any other medium that may be used to store desired information and that may be accessed by the processor.

[0106] The memory may be a non-transitory computer-readable medium. As used herein, the term "computer-readable medium" (or "machine-readable medium") is an extensible term that refers to any medium or any memory involved in providing instructions to a processor for execution, or any mechanism for storing or transmitting information in a form readable by a machine (e.g., a computer). Such media may store computer-executable instructions executed by the processing elements and / or control logic, as well as data operated on by the processing elements and / or control logic, and may take many 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. The instructions may be in the form of an algorithm, program logic, etc. that causes the processor to perform any of the functions disclosed herein.

[0107] Aspects of the memory may include processor modules and other circuitry to enable transfer of data to and from the memory, which may include to and from other components of the communication system. This transfer may occur via wired or wireless transmission. The communication system may include transceivers, which may be used in combination with switches, receivers, transmitters, routers, gateways, waveguides, etc. to facilitate communication via a communication approach or protocol for controlled and coordinated signal transmission and processing to any other component or combination of components of the communication system. The transmission may occur via a communication link. The communication link may be electronic-based, optical-based, optoelectronic-based, quantum-based, etc. The communication may occur via Bluetooth, near-field communication, cellular communication, telemetry communication, internet communication, etc.

[0108] Data and signals may be transmitted over a transmission medium. Transmission media may include coaxial cables, copper wire, fiber optics, and the like. Transmission media may also take the form of acoustic or light waves, such as those generated during radio wave and infrared data communications, or other forms of propagated signals (e.g., carrier waves, digital signals, etc.).

[0109] Any processor may communicate with other processors of other devices (e.g., computing devices, computing systems, laptop computers, desktop computers, etc.). Any processor may have a transceiver or other communication device / circuitry to facilitate 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 communicate with each other.

[0110] Another exemplary embodiment can be a method for selecting a treatment for a human subject suffering from androgenetic alopecia.The method can include measuring sulfotransferase activity in a patient sample to generate an activity value that indicates a biochemical activation response to minoxidil (which in some embodiments can include SULT1A1 gene expression and / or SULT1A1 gene variant expression in the sample).The method can include comparing the activity value with a standard activity value.The method can include predicting a response to treatment with minoxidil based on the comparison.The method can include prescribing a minoxidil dosage, a minoxidil administration frequency, and / or a minoxidil administration routine as androgenetic alopecia treatment.

[0111] In some embodiments, prescribing a minoxidil dosage, a minoxidil dosage frequency, and / or a minoxidil dosage routine can include prescribing oral minoxidil or topical minoxidil.

[0112] In some embodiments, predicting the response to treatment with minoxidil can include presuming that the patient will respond well to oral minoxidil if the activity value is below the threshold standard activity value and presuming that the patient will not respond well to oral minoxidil if the activity value is above the threshold standard activity value.

[0113] In some embodiments, a prescription for treatment of androgenetic alopecia may include prescribing topical minoxidil when activity levels are below a threshold standard activity level and not prescribing oral minoxidil when activity levels are above a threshold standard activity level.

[0114] The above are exemplary ways of implementing the invention and are not intended to be limiting. It will be apparent to those skilled in the art that modifications can be made without departing from the spirit and scope of the invention as set forth in the following claims. [Explanation of symbols]

[0115] 100 ways 102 Hair follicle collection 104 Associated with a unique identifier 106 Analyze 108 results provided 200 Systems 202 Sample 204 Laboratory 206 Computer Systems 208 Computer Systems 210 Internet 212 Server

Claims

1. A method for predicting response to minoxidil, comprising: measuring gene activity, genetic activity, and / or enzyme activity in the patient sample to generate an activity value indicative of a biochemical activation response to minoxidil; comparing said activity value with a standard activity value; and Predicting a response to treatment with minoxidil based on said comparison.

2. Measuring gene activity, genetic activity, and / or enzyme activity Measuring SULT1A1 gene expression, SULT1A1 gene variant expression, and / or SULT1A1 enzyme activity in the sample; Measuring SLC22A9 gene expression, SLC22A9 gene variant expression, SLC22A9 transporter activity from hair cells in the sample; and / or measuring SLC22A9 transporter activity; Measuring AABC3 gene expression and / or AABC3 gene variant expression in the sample; and / or Measuring the patient's blood flow Including, The method of claim 1.

3. The minoxidil treatment is oral minoxidil treatment; The method of claim 1.

4. Predicting response to treatment with minoxidil Where the gene activity, genetic activity, and / or enzymatic activity is associated with SULT1A1, predicting that a patient will respond to oral minoxidil treatment if the activity value is below a threshold standard activity value; predicting that a patient will not respond adequately to oral minoxidil treatment if the activity value is greater than the threshold standard activity value; If the gene activity, genetic activity and / or SLC22A9 transporter activity from hair cells is related to SLC22A9, predicting that a patient will respond to oral minoxidil treatment if the activity value is greater than the threshold standard activity value; It is presumed that a patient will not respond adequately to oral minoxidil treatment if the activity value is below the threshold standard activity value; Where the gene activity and / or genetic activity is associated with AABC3, predicting that a patient will respond to oral minoxidil treatment if the activity value is below a threshold standard activity value; Presuming that a patient will not respond adequately to oral minoxidil treatment if the activity level is higher than the threshold standard activity level Including, The method of claim 2.

5. Measuring blood flow in the patient includes Doppler velocimetry; Predicting response to treatment with minoxidil predicting that the patient will respond well to oral minoxidil treatment if the Doppler velocity is below a threshold; and predicting that said patient will not respond adequately to oral minoxidil treatment if said Doppler velocity is greater than said threshold value. Including, The method of claim 1.

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

7. Where the gene activity, genetic activity, and / or enzymatic activity relates to SULT1A1, predicting that patients will respond well to oral minoxidil treatment if their activity is below a threshold standard activity value that is within the range of 0.37 to 0.4; A patient is predicted to not respond adequately to oral minoxidil treatment if the activity is greater than a threshold standard activity value within the range of 0.37 to 0.

4. The method of claim 1.

8. Treatment with minoxidil is a treatment for androgenetic alopecia; The method of claim 1.

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

10. Response to treatment with minoxidil is increased or improved hair growth or hair retention; The method of claim 1.

11. predicting the response to treatment with minoxidil includes estimating a biochemical activation response based on a minoxidil dosage, a minoxidil dosage frequency, and / or a minoxidil dosage routine; The method of claim 1.

12. The standard activity value relates to a biochemical activation response to minoxidil associated with hair growth or hair retention for a class of individuals. The method of claim 1.

13. The standard activity value relates to a biochemical activation response to minoxidil associated with hair growth or hair retention, where a statistical sample of subjects exhibits a high or low minoxidil response to a minoxidil dosage, a minoxidil dosing frequency, and / or a minoxidil dosing routine. The method of claim 1.

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

15. Measuring gene activity, genetic activity, and / or enzyme activity in a patient sample is performed before, during, and / or after the patient is treated with minoxidil. The method of claim 1.

16. Measuring sulfotransferase activity in a patient sample is performed 1 to 14 days before the patient is treated with minoxidil. The method of claim 1.

17. Measuring gene activity, genetic activity, and / or enzyme activity in the patient sample is performed via an assay device; The method of claim 1.

18. Measuring gene activity, genetic activity, and / or enzyme activity in the patient sample is performed via a colorimetric assay device; The method of claim 1.

19. Predicting response to treatment with minoxidil includes implementing a neural network. The method of claim 1.

20. 10. The method of claim 1, wherein measuring gene activity, genetic activity, and / or enzymatic activity in a patient sample comprises obtaining one or more hair follicles and / or one or more scalp biopsies as samples, and measuring gene activity, genetic activity, and / or enzymatic activity in the patient sample is performed via an assay device, the method comprising: placing said 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 length of time; and Stopping the reaction. A method comprising:

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

22. Measuring gene activity, genetic activity, and / or enzyme activity Measuring SULT1A1 gene expression, SULT1A1 gene variant expression, and / or SULT1A1 enzyme activity in the sample; Measuring SLC22A9 gene expression, SCL22A9 gene variant expression, SLC22A9 transporter activity from hair cells in said sample, and / or SCL22A9 transporter activity; Measuring AABC3 gene expression and / or AABC3 gene variant expression in said sample; and / or Measuring the patient's blood flow Including, 22. The method of claim 21.

23. Prescribing a minoxidil dosage, a minoxidil dosage frequency, and / or a minoxidil dosage routine includes prescribing oral minoxidil.

22. The method of claim 21.

24. Measuring blood flow in the patient includes Doppler velocimetry; Predicting response to treatment with minoxidil predicting that the patient will respond well to oral minoxidil treatment if the Doppler velocity is below a threshold; and predicting that said patient will not respond adequately to oral minoxidil treatment if said Doppler velocity is greater than said threshold value. Including, 22. The method of claim 21.

25. Predicting response to treatment with minoxidil Where the gene activity, genetic activity, and / or enzymatic activity is associated with SULT1A1, predicting that a patient will respond to oral minoxidil treatment if the activity value is below a threshold standard activity value; predicting that a patient will not respond adequately to oral minoxidil treatment if the activity value is greater than the threshold standard activity value; If the gene activity, genetic activity and / or SLC22A9 transporter activity from hair cells is related to SLC22A9, predicting that a patient will respond to oral minoxidil treatment if the activity value is greater than the threshold standard activity value; It is presumed that a patient will not respond adequately to oral minoxidil treatment if the activity value is below the threshold standard activity value; Where the gene activity and / or genetic activity is associated with AABC3, predicting that a patient will respond to oral minoxidil treatment if the activity value is below a threshold standard activity value; Presuming that a patient will not respond adequately to oral minoxidil treatment if the activity level is higher than the threshold standard activity level Including, 22. The method of claim 21.

26. Where the gene activity, genetic activity, and / or enzymatic activity relates to SULT1A1, predicting that patients will respond well to oral minoxidil treatment if their activity is below a threshold standard activity value that is within the range of 0.37 to 0.4; 22. The method of claim 21, wherein the patient is predicted to not respond adequately to oral minoxidil treatment if the activity value is greater than a threshold standard activity value that is within the range of 0.37 to 0.

4.

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

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