ISOTOPICALLY MODIFIED COMPOSITION AND THERAPEUTIC USES THEREOF
Isotopically modified polyunsaturated fatty acid or ester thereof, such as 11,11-D2-linoleic acid or its ethyl ester, and uses of the same for treating or ameliorating the symptoms of Friedreich's ataxia arm disclosed.
1 . A method of treating a subject having Friedreich's ataxia, comprising:
selecting a subject having Friedreich's ataxia; and
administering an effective amount of 11,11-D2-linoleic acid or an ester thereof to the subject in need thereof.
2 . The method of claim 1 , wherein the subject having Friedreich's ataxia has mutations in the frataxin (FXN) gene.
3 . The method of claim 2 , wherein the mutations comprise an expanded GAA repeat mutation in the FXN gene.
4 . The method of any one of claims 1 to 3 , wherein the subject has a FARS-Neuro score from about 20 to about 100.
5 . The method of any one of claims 1 to 3 , wherein the subject has a body mass index (BMI) from about 15 kg/m 2 to about 35 kg/m 2 .
6 . The method of anyone of claims 1 to 5 , wherein the 11,11-D2-linoleic acid ester is an ethyl ester.
7 . The method of anyone of claims 1 to 6 , wherein the amount of 11,11-D2-linoleic acid or the ester thereof is from about 1 g to about 10 g.
8 . The method of claim 7 , wherein the amount of 11,11-D2-linoleic acid or the ester thereof is from about 2 g to about 5 g.
9 . The method of any one of claims 1 to 8 , wherein 11,11-D2-linoleic acid or the ester thereof is administered once per day.
10 . The method of any one of claims 1 to 8 , wherein 11,11-D2-linoleic acid or the ester thereof is administered two or more times per day.
11 . The method of any one of claims 1 to 10 , wherein the amount of 11,11-D2-linoleic acid or the ester thereof is from about 1 g to about 20 g per day.
12 . The method of claim 11 , wherein the amount of 11,11-D2-linoleic acid or the ester thereof is from about 2 g to about 10 g per day.
13 . The method of any one of claims 1 to 12 , wherein 11,11-D2-linoleic acid or the ester thereof is administered for at least 2, 3, or 4 weeks.
14 . The method of any one of claims 1 to 13 , wherein the steady state plasma 24-hour AUC of 11,11-D2-linoleic acid or the ester thereof is from about 1000 μg*h/mL to about 8000 μg*h/mL.
15 . The method of any one of claims 1 to 14 , further comprising detecting a metabolite of 11,11-D2-linoleic acid or the ester thereof in the plasma.
16 . The method of claim 15 , wherein the metabolite is 13,13-D2-arachidonic acid.
17 . The method of claim 16 , wherein the steady state plasma concentration of 13,13-D2-arachidonic acid is from about 2 μg/mL to about 40 μg/mL.
18 . The method of any one of claims 1 to 13 , further comprising detecting 11,11-D2-linoleic acid or the ester thereof inside the red blood cells (RBCs).
19 . The method of claim 18 , wherein the steady state RBC concentration of 11,11-D2-linoleic acid or the ester thereof is from about 5 μg/mL to about 75 μg/mL.
20 . The method of claim 19 , wherein the RBC concentration of 11,11-D2-linoleic acid or the ester thereof is about 5% to about 30% of total linoleic acid or the ester thereof.
21 . The method of any one of claims 1 to 20 , wherein the method improves one or more parameters selected from the group consisting of VO 2 max, FARS-neuro, cardiopulmonary exercise testing (CPEP), peak workload, and timed 25-foot walk (T25FW).
22 . The method of any one of claims 1 to 21 , wherein the subject also ingests a non-isotopically modified polyunsaturated fatty acid, a non-isotopically modified polyunsaturated fatty acid ester, or a combination thereof.
23 . The method of claim 22 , wherein the amount of 11,11-D2-linoleic acid or the ester thereof is about 5% or greater of the total amount of the polyunsaturated fatty acids and polyunsaturated fatty acid esters delivered to the subject.
24 . The method of claim 22 , wherein the amount of the 11,11-D2-linoleic acid or the ester thereof is equal to less than about 1% of the total amount of the polyunsaturated fatty acids and polyunsaturated fatty acid esters delivered to the subject.
25 . The method of any one of claims 1 to 24 , wherein 11,11-D2-linoleic acid or the ester thereof is administered with food.
26 . The method of any one of claims 1 to 24 , wherein 11,11-D2-linoleic acid or the ester thereof is administered between meals.
27 . The method of any one of claims 1 to 26 , wherein 11,11-D2-linoleic acid or the ester thereof is administered with at least one antioxidant.
28 . The method of claim 27 , wherein the antioxidant is selected from the group consisting of Coenzyme Q, idebenone, mitoquinone, mitoquinol, vitamin E, and vitamin C, and combinations thereof.