Methods for Inhibiting the Development of Huntington's Disease

• US 20110077226A1
• Filed: 12/06/2010
• Published: 03/31/2011
• Est. Priority Date: 09/04/2002
• Status: Active Grant

• Current Assignee: James A. Carnazza
• Original Assignee: James A. Carnazza
• Inventors: Carnazza, James A.
• Granted Patent: US 8,895,541 B2
• Time in Patent Office: Days
• US Class Current: 514/170
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/568 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: G01N 2333/575 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin G01N2333/665, corticotropin G01N2333/695
• CPC Class Codes: G01N 2800/2835 Movement disorders, e.g. Parkinson, Huntington, Tourette
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease
• CPC Class Codes: G01N 33/743 Steroid hormones

Abstract

This invention relates to Huntington'"'"'s disease and more specifically to methods for inhibiting the development of or treating Huntington'"'"'s disease by administering estrogen, testosterone, precursors thereof or combinations thereof.

Claims

1. A method of treating a female individual having Huntington'"'"'s Disease (HD) or a HD gene having greater than or equal to about 36 CAG repeats;

the method comprises;

a. selecting a female individual having HD or a HD gene having greater than or equal to about 36 CAG repeats; and

b. administering to the female individual an amount of estrogen, a precursor thereof, or a combination thereof, wherein the amount of administration to the female individual ranges from about 0.025 mg to about 10 mg;

wherein the female individual with HD or HD gene having greater than or equal to about 36 CAG repeats is treated.

2. The method of claim 1, further comprising measuring levels of estrogen, a precursor thereof, or a combination thereof in the female individual.

3. The method of claim 1, wherein the female individual has greater than 40 CAG repeats.

4. The method of claim 3, wherein the female individual has between about 36 and about 120 CAG repeats.

5. The method of claim 1, wherein one or more symptoms of HD is reduced, wherein the symptoms of HD comprise weight loss, loss of fine or gross motor function, a loss in cognitive function, chorea, or loss of brain tissue or a combination thereof.

6. The method of claim 5, wherein one or more of the symptoms are reduced by a range between about 5% and about 100%.

7. The method of claim 5, wherein the Unified Huntington'"'"'s Disease Rating Scale (UHDRS) score remains the same or does not increase.

8. The method of claim 1, wherein selecting a female individual having HD comprises assessing the presence or absence of a mutant HD gene having between about 36 and 120 CAG repeats.

16. The method of claim 1, wherein selecting a male individual having HD comprises assessing the presence or absence of a mutant HD gene having between about 36 and 120 CAG repeats.

9. A method of treating a male individual having HD or a HD gene having greater than or equal to about 36 CAG repeats;

the method comprises;

a. selecting a male individual having HD or a HD gene having greater than or equal to about 36 CAG repeats; and

b. administering to a male individual an amount of testosterone, a precursor thereof, or a combination thereof, wherein the amount of administration of a male individual ranges from about 1 mg to about 35 g;

wherein the male individual with HD or HD gene having greater than or equal to about 36 CAG repeats is treated.

10. The method of claim 9, further comprising measuring levels of testosterone, a precursor thereof, or a combination thereof in the individual.

11. The method of claim 9, wherein the male individual has greater than 40 CAG repeats.

12. The method of claim 11, wherein the male individual has between about 36 and about 120 CAG repeats.

13. The method of claim 9, wherein one or more symptoms of HD is reduced, wherein the symptoms of HD comprise weight loss, loss of fine or gross motor function, a loss in cognitive function, chorea, or loss of brain tissue or a combination thereof.

14. The method of claim 13, wherein one or more of the symptoms are reduced by a range between about 5% and about 100%.

15. The method of claim 13, wherein the UHDRS score remains the same or does not increase.

17. A method of reducing one or more symptoms associated with HD in a female individual, wherein the method comprises:

a. selecting the female individual having HD; and

b. administering to the female individual an amount of estrogen, a precursor thereof, or a combination thereof, wherein the amount of administration to a female individual ranges from about 0.025 mg to about 10 mg;

wherein one or more symptoms associated with HD in the female individual is reduced, as compared to an individual with HD not subjected to step b.

18. The method of claim 17, wherein the symptoms of HD comprises weight loss, loss of fine or gross motor function, a loss in cognitive function, chorea, loss of brain tissue, or a combination thereof.

19. The method of claim 18, wherein one or more symptoms are reduced by an amount between about 5% and about 100%.

20. A method of reducing one or more symptoms associated with HD in a male individual, wherein the method comprises:

a. selecting the male individual having HD; and

b. administering to the male individual an amount of testosterone, a precursor thereof, or a combination thereof, wherein the amount of administration of a male individual ranges from about 1 mg to about 35 g;

wherein one or more symptoms associated with HD in the male individual is reduced, as compared to an individual with HD not subjected to step b.

21. The method of claim 20, wherein the symptoms of HD comprises weight loss, loss of fine or gross motor function, a loss in cognitive function, chorea, loss of brain tissue, or a combination thereof.

22. The method of claim 21, wherein one or more symptoms are reduced by an amount between about 5% and about 100%.

23. A method of preventing weight loss, or reducing the amount of weight loss in a female individual having HD, wherein the method comprises:

a. selecting the female individual having HD; and

b. administering to the female individual an amount of estrogen, a precursor thereof, or a combination thereof, wherein the amount of administration to a female individual ranges from about 0.025 mg to about 10 mg;

wherein weight loss is prevented or the amount of weight loss is reduced in the female individual with HD, as compared to an individual with HD not subjected to step b.

24. The method of claim 23, wherein the amount of weight loss is reduced by between about 5% and about 100%.

25. The method of claim 23, wherein selecting the female individual having HD comprises assessing for the presence or absence of a mutant huntingin protein having a polyglutamine tract, or mutant HD gene having a CAG repeat.

26. A method of preventing weight loss, or reducing the amount of weight loss in a male individual having HD, wherein the method comprises:

a. selecting the male individual having HD; and

b. administering to the male individual an amount of testosterone, a precursor thereof, or a combination thereof, wherein the amount of administration ranges from about 1 mg to about 35 g;

wherein weight loss is prevented or the amount of weight loss is reduced in the male individual with HD, as compared to an individual with HD not subjected to step b.

27. The method of claim 26, wherein the amount of weight loss is reduced by between about 5% and about 100%.

28. The method of claim 26, wherein selecting the male individual having HD comprises assessing for the presence or absence of a mutant huntingin protein having a polyglutamine tract, or mutant HD gene having a CAG repeat.

29. A method of treating a female individual having HD, the method comprises:

a. assessing the female individual for the presence or absence of HD or the presence of absence of a HD gene having between about 36 CAG repeats and about 120 CAG repeats;

b. assessing one or more levels of estrogen, precursors thereof, or a combination thereof in the female individual to determine if the one or more levels is below a normal level; and

c. administering to the female individual an amount of estrogen, a precursor thereof, or a combination thereof to maintain an average amount of estrogen at a level in the female individual between about 100 pg/ml to about 185 pg/ml.

30. The method of claim 29, wherein the estrogen, or a combination thereof is administered periodically, daily, or weekly.

31. A method of treating an male individual having HD, the method comprises:

a. assessing the male individual for the presence or absence of HD or the presence of absence of a HD gene having between about 36 CAG repeats and about 120 CAG repeats;

b. assessing one or more levels of testosterone, precursors thereof, or a combination thereof in the male individual to determine if the one or more levels is below a normal level; and

c. administering to the male individual an amount of testosterone, a precursor thereof, or a combination thereof to maintain an average of free testosterone at a level in the male individual between about 20 pg/ml to about 40 pg/ml, total testosterone is between 300 ng/dL and about 900 ng/dL, or both.

32. The method of claim 31, wherein the estrogen, testosterone, or a combination thereof is administered periodically, daily, or weekly.

33. A method of treating a female individual having a trinucleotide repeat disorder, the method comprises:

a. selecting the female individual having a trinucleotide repeat disorder; and

b. administering to the female individual an amount of estrogen, precursors thereof or a combination thereof;

wherein the female individual having a trinucleotide repeat disorder is treated.

34. The method of claim 33, wherein a trinucleotide repeat disorder comprises HD, Dentatorubropallidoluysian atrophy, Kennedy disease, Spinocerebellar ataxia (SA) Type 1, SA Type 2, SA Type 3, SA Type 6, SA Type 7, and SA Type 17.

35. A method of treating a male individual having a trinucleotide repeat disorder, the method comprises:

a. selecting the male individual having a trinucleotide repeat disorder; and

b. administering to the male individual an amount of testosterone, precursors thereof or a combination thereof;

wherein the male individual having a trinucleotide repeat disorder is treated.

36. The method of claim 35, wherein a trinucleotide repeat disorder comprises HD, Dentatorubropallidoluysian atrophy, Kennedy disease, Spinocerebellar ataxia (SA) Type 1, SA Type 2, SA Type 3, SA Type 6, SA Type 7, and SA Type 17.

37. A method of inhibiting a mutant huntingtin protein in a female individual having HD, wherein the method comprises:

administering to the female individual an amount of estrogen, a precursor thereof or a combination thereof;

wherein the mutant huntingtin protein is inhibited.

38. The method of claim 37, wherein estrogen binds the mutant huntingtin protein.

39. The method of claim 37, further including assessing the presence or absence of the mutant huntingtin protein or an HD gene having greater than or equal to 36 CAG repeats.

40. A method of inhibiting a mutant huntingtin protein in a male individual having HD, wherein the method comprises:

administering to the male individual an amount of testosterone, a precursor thereof or a combination thereof;

wherein the mutant huntingtin protein is inhibited.

41. The method of claim 40, wherein testosterone is converted to estrogen in brain tissue and the converted estrogen binds the mutant huntingtin protein.

42. The method of claim 40, further including assessing the presence or absence of the mutant huntingtin protein or an HD gene having greater than or equal to 36 CAG repeats.

43. A method of treating a female individual having HD, the method comprises:

a. assessing a female individual for the presence or absence of HD or the presence of absence of a HD gene having between about 36 CAG repeats and about 120 CAG repeats to thereby obtain a female individual with HD;

b. assessing a level of estrogen in the female individual to determine if the level of estrogen is below about 100 pg/ml; and

c. administering to the female individual having HD and a level of estrogen below about 100 pg/ml, an amount of estrogen, a precursor thereof or a combination thereof, wherein the amount of administration to a female individual ranges from about 0.025 mg to about 10 mg;

wherein the female individual with HD is treated.

44. A method of treating a male individual having HD, the method comprises:

a. assessing a male individual for the presence or absence of HD or the presence of absence of a HD gene having between about 36 CAG repeats and about 120 CAG repeats to thereby obtain a male individual with HD;

b. assessing one or more levels of testosterone in the male individual to determine if the level of free testosterone is below about 20 pg/ml, or the level of total testosterone is below about 300 ng/dL; and

c. administering to the male individual having HD and a level of free testosterone is below about 20 pg/ml, or the level of total testosterone is below about 300 ng/dL, an amount of testosterone, a precursor thereof or a combination thereof, wherein the amount of administration to a male individual ranges from about 1 mg to about 35 g;

wherein the male individual with HD is treated.