Combination therapy with acetyl-leucine and miglustat
The present disclosure provides methods of treating lysosomal storage disorders (LSDs) in a subject in need thereof by administering a combination of acetyl-leucine and miglustat to the subject, wherein subject is naive to treatment with miglustat.
1 . A method of reducing, or ameliorating Niemann-Pick Disease Type C, or a symptom thereof, in a subject in need thereof, the method comprising administering a combination of:
(i) a therapeutically effective amount of acetyl-leucine; and
(ii) a therapeutically effective amount of miglustat,
to the subject, wherein the subject is naive to treatment with miglustat, and the combination of acetyl-leucine and miglustat reduces weight loss associated with the administration of miglustat.
2 . The method of claim 1 , wherein acetyl-leucine and miglustat are administered simultaneously.
3 . The method of claim 2 , wherein acetyl-leucine and miglustat are administered as a single pharmaceutical formulation.
4 . The method of claim 2 , wherein acetyl-leucine and miglustat are administered as two separate pharmaceutical formulations.
5 . The method of claim 1 , wherein acetyl-leucine and miglustat are administered sequentially.
6 . The method of claim 5 , wherein acetyl-leucine is administered before miglustat.
7 . The method of claim 5 , wherein acetyl-leucine is administered after miglustat.
8 . The method of claim 5 , wherein acetyl-leucine and miglustat are administered about 1 minute to about 6 hours apart.
9 . The method of claim 8 , wherein acetyl-leucine and miglustat are administered about 1 minute to 3 hours apart.
10 . The method of claim 9 , wherein acetyl-leucine and miglustat are administered about 1 minute to 1 hour apart.
11 . The method of claim 1 , wherein acetyl-leucine and miglustat are administered orally.
12 . The method of claim 1 , wherein acetyl-leucine is administered once, twice, or three times per day.
13 . The method of claim 1 , wherein miglustat is administered once, twice, or three times per day.
14 . The method of claim 1 , wherein about 3 g to about 15 g of acetyl-leucine is administered per day.
15 . The method of claim 1 , wherein about 0.05 g to about 2 g of miglustat is administered per day.
16 . The method of claim 1 , wherein acetyl-leucine and miglustat are administered as a first-line therapy to treat Niemann-Pick Disease Type C, or a symptom thereof.
17 . The method of claim 1 , wherein the acetyl-leucine is N-acetyl-DL-leucine.
18 . The method of claim 1 , wherein the acetyl-leucine is N-acetyl-L-leucine.
19 . The method of claim 1 , wherein the combination of acetyl-leucine and miglustat reduces appetite suppression associated with the administration of miglustat.
20 . A kit for carrying out the method of claim 1 , the kit comprising acetyl-leucine and miglustat for treating Niemann-Pick Disease Type C, or a symptom thereof, in a subject.
21 . The kit of claim 20 further comprising instructions for administering the acetyl-leucine and miglustat to the subject.