Pharmaceutical compositions and uses directed to lysosomal storage disorders
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Publication Number
US-11400067-B2
Publication Date
2022-08-02
Expiration Date
Abstract
The present disclosure provides for treating lysosomal storage disorders (LSDs) comprising administering acetyl-leucine or a pharmaceutically acceptable salt thereof.
Core Innovation
The document discloses treatment of lysosomal storage disorders (LSDs) and one or more LSD-associated symptoms using acetyl-leucine, including a racemate or L- or D-enantiomer, and pharmaceutically acceptable salts. It provides a broad set of target LSDs selected from named disorders and describes treatment of a subject in need thereof, including situations where the subject is asymptomatic, with acetyl-leucine administered for durations selected from at least about 3 months, at least about 6 months, at least about 1 year, at least about 2 years, and at least about 5 years.
The disclosure includes therapeutic goals tied to acetyl-leucine administration, including treating, delaying onset, delaying progression, and reversing progression of an LSD over time, as well as improving biochemical markers. It also describes reducing severity of an LSD and reducing or eliminating one or more existing symptoms, while excluding Niemann-Pick Type C for at least one described method.
The document further supports the disclosed approaches with examples in an NPC disease context and other LSD models, including phenotypic and mechanistic data. Reported effects include reduced lysosomal volume in patient fibroblasts measured using LysoTracker, reduced glycosphingolipid storage in GM2 gangliosidosis fibroblasts, and increased lifespan and improved motor function in Sandhoff mice. It also describes patient case studies using clinical severity measures including SARA/SCAFI and NPC CSS/ASIS showing symptom stabilization or improvement with long-duration acetyl-leucine therapy.
Claims Coverage
The partial claim set provided includes seven independent claims, covering therapeutic treatment, delaying progression, reversing progression, improving biochemical markers, reducing severity or eliminating symptoms, and providing neuroprotection. Across these independent claims, the inventive features center on acetyl-leucine (or a pharmaceutically acceptable salt) administered for specified minimum durations, with additional constraints on target LSD scope, patient state, biochemical marker definition, and exclusion of Niemann-Pick Type C in at least two claims.
Acetyl-leucine administration for treating an LSD or symptoms for extended durations
Administering a therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof to a subject for a duration chosen from at least about 3 months, at least about 6 months, at least about 1 year, at least about 2 years, and at least about 5 years, wherein the LSD is chosen from Niemann-Pick type C disease, Tay-Sachs disease, the AB variant of Tay-Sachs disease, Sandhoff disease, Niemann-Pick type A disease, Niemann-Pick type B disease, Fabry disease, neuronal ceroid lipofuscinoses, Krabbe disease, Farber disease, Gaucher disease, metachromatic leukodystrophy, multiple sulphatase deficiency, mucolipidosis II, mucolipidosis III, MPS III, MPS VII, GM1 gangliosidosis, and aspartylglucosaminuria.
Delaying progression of an LSD by acetyl-leucine administration over time
Administering a therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof to the subject for a duration chosen from at least about 3 months, at least about 6 months, at least about 1 year, at least about 2 years, and at least about 5 years.
Reversing progression of an LSD by acetyl-leucine administration over time
Administering a therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof to the subject for a duration chosen from at least about 3 months, at least about 6 months, at least about 1 year, at least about 2 years, and at least about 5 years.
Improving a biochemical marker of an LSD by acetyl-leucine administration for extended durations
Administering a therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof to the subject for a duration chosen from at least about 3 months, at least about 6 months, at least about 1 year, at least about 2 years, and at least about 5 years, wherein the biochemical marker of a lysosomal storage disorder (LSD) is improved over time.
Reducing severity of an LSD or eliminating symptoms using acetyl-leucine with Niemann-Pick Type C excluded
Administering a therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof to the subject, wherein the LSD is not Niemann-Pick Type C.
Providing neuroprotection for an LSD subject using acetyl-leucine for extended durations
Administering a therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof to the subject for a duration chosen from at least about 3 months, at least about 6 months, at least about 1 year, at least about 2 years, and at least about 5 years.
Delaying or reversing progression, or reducing severity, in an asymptomatic subject with Niemann-Pick Type C excluded
Administering a therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof to the subject, wherein the LSD is not Niemann-Pick Type C and the subject is asymptomatic.
Across the independent claims, the core inventive coverage is methods that administer acetyl-leucine (or a pharmaceutically acceptable salt) to a subject in need thereof, including for minimum treatment durations extending to at least about 5 years. The claims further distinguish purposes (treating, delaying, reversing, improving biochemical markers, reducing severity or symptoms, and neuroprotection) and impose constraints including exclusion of Niemann-Pick Type C and a requirement for an asymptomatic subject in at least one method.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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