METHODS FOR TREATING PARKINSON'S DISEASE WITH SEPIAPTERIN

1 . A method of treating Parkinson's disease in a subject in need thereof, the method comprising administering to the subject an effective amount of sepiapterin, or a pharmaceutically acceptable salt thereof.

2 . The method of claim 1 , comprising administering to the subject an effective amount of sepiapterin, or a pharmaceutically acceptable salt thereof, with food.

3 . The method of claim 1 , comprising administering to the subject an effective amount of sepiapterin, or a pharmaceutically acceptable salt thereof, without food.

4 . A method of treating Parkinson's disease in a subject in need thereof, the method comprising administering to the subject an effective amount of sepiapterin, or a pharmaceutically acceptable salt thereof, once per day.

5 . A method of treating Parkinson's disease in a subject in need thereof, the method comprising administering to the subject an effective amount of sepiapterin, or a pharmaceutically acceptable salt thereof, more than once per day.

6 . A method of treating Parkinson's disease in a subject in need thereof, the method comprising administering about 50 mg/kg to about 100 mg/kg of sepiapterin per day, or a pharmaceutically acceptable salt thereof to the subject.

7 . A method of treating Parkinson's disease in a subject in need thereof, the method comprising administering to the subject an effective amount of sepiapterin, or pharmaceutically acceptable salt thereof, in with combination with at least one other agent used to treat Parkinson's disease.

8 . The method of any one of claims 1 or 5 - 7 , wherein the method comprises administering to the subject an effective amount of sepiapterin, or a pharmaceutically acceptable salt thereof, with food twice per day.

9 . The method of any one of claims 1 or 5 - 7 , wherein the method comprises administering to the subject an effective amount of sepiapterin, or a pharmaceutically acceptable salt thereof, without food twice per day.

10 . The method of any one of claims 1 to 9 , wherein the effective amount is an amount sufficient to produce a BH4 concentration of at least 50 ng/mL in the plasma of the subject within 10 hours of administration.

11 . The method of claim 2 , wherein the effective amount comprises a dose that is at least 20% lower than the dose sufficient to produce a maximum BH4 plasma concentration (C max ) of at least 50 ng/mL in the plasma of the subject within 10 hours of administration of sepiapterin, or a pharmaceutically acceptable salt thereof, without food.

12 . The method of any one of claims 1 to 11 , wherein the effective amount is 2.5 mg/kg to 100 mg/kg per dose.

13 . The method of any one of claims 1 to 2 , 4 to 8 , or 10 to 12 , wherein the administration to the subject occurs less than 30 minutes prior to consuming food.

14 . The method of any one of claims 1 to 2 , 4 to 8 , or 10 to 12 , wherein the administration to the subject is substantially at the same time as food.

15 . The method of any one of claims 1 to 2 , 4 to 8 , or 10 to 12 , wherein the administration is immediately after the consumption of food up to 2 hours after the consumption.

16 . The method of any one of claims 1 , 3 to 7 , 9 to 10 , or 12 , wherein the administration to the subject occurs more than 30 minutes prior to consuming food.

17 . The method of any one of claims 1 , 3 to 7 , 9 to 10 , 12 , or 16 , wherein the administration is more than 2 hours after the consumption of food.

18 . The method of any one of claims 1 to 17 , wherein the effective amount results in an increase in the level of homovanillic acid and/or 5-hydroxyindoleacetic acid in the CSF of the subject.

19 . The method of any one of any one of claims 1 to 18 , wherein the level of homovanillic acid and/or 5-hydroxyindoleacetic acid in the subject is increased at least 100% compared to the level prior to administration.

20 . The method of any one of claims 1 to 19 , wherein the effective amount results in an increase in the level of serotonin and/or dopamine in the CSF of the subject.

21 . The method of any one of claims 1 to 20 , wherein the level of serotonin and/or dopamine in the subject is increased at least 100% compared to the level prior to administration.

22 . The method of any one of claims 1 to 21 , wherein the sepiapterin or a pharmaceutically acceptable salt thereof is formulated as an oral powder for suspension.

23 . The method of any one of claims 1 to 22 , wherein the sepiapterin or a pharmaceutically acceptable salt thereof is administered as a suspension in Medisca Oral Mix.

24 . The method of any one of claims 1 to 23 , wherein the method further comprises administering an effective amount of levodopa to the subject.

25 . The method of any one of claims 1 to 24 , wherein the method further comprises administering an effective amount of carbidopa to the subject.

26 . The method of any one of claims 1 to 25 , wherein the method further comprises administering an effective amount of an AADC inhibitor, an AADC gene therapy, a COMT inhibitor, a dopamine agonist, a MAO-B inhibitor, a DAT inhibitor, a NMDA antagonist, an anticholinergic agent, and/or an acetylcholinesterase inhibitor.

27 . The method of any one of claims 1 to 26 , wherein the effective amount of sepiapterin comprises 60 mg/kg per day.

28 . The method of claim 27 , wherein the 60 mg/kg per day is administered in two equal doses of 30 mg/kg.

29 . The method of claim 27 , wherein the 60 mg/kg per day is administered in two unequal doses of 40 mg/kg and 20 mg/kg.

30 . The method of claim 28 , wherein the two equal doses are administered with a morning meal and with an evening meal.

31 . The method of claim 29 , wherein the two unequal doses are administered with a morning meal and with an evening meal.

32 . The method of any one of claims 1 to 31 , wherein the administration results in an improvement in the MDS-UPDRS of the subject.

33 . The method of any one of claims 1 to 32 , wherein the administration results in a decrease in the Total Daily OFF Time in the subject.

34 . The method of any one of claims 1 to 33 , wherein the administration results in an improvement in the Hamilton Depression Rating Scale in the subject.

35 . The method of any one of claims 1 to 34 , wherein the results in an improvement in the Parkinson's Disease Sleep Scale in the subject.