Treatment of CNS disorders associated with mutations in genes encoding lysosomal enzymes
View Patent ↗Described is a method for treating an individual having a neurological disorder with an associated mutation or mutations in a gene encoding a lysosomal enzyme. Specifically, the individual is administered a specific pharmacological chaperone for the lysosomal enzyme which increases trafficking of the protein from the ER to the lysosome in neural cells, with or without concomitantly increasing enzyme activity in neural cells. Restoration of trafficking relieves cell stress and other toxicities associated with accumulation of mutant proteins. Restoration of enzyme activity relieves substrate accumulation and pathologies associated with lipid accumulation. In a specific embodiment, the neurological disorder is Parkinson's disease or parkinsonism which is associated with mutations in glucocerebrosidase.
1. A method for treating Parkinson's disease or parkinsonism in an individual, which method comprises administering to the individual an effective amount of (5R, 6R, 7S, 8S)-5-hydroxymethyl-2-octyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-6,7,8-triol.
2. The method of claim 1 , wherein Parkinson's disease is early-onset Parkinson's disease.
3. The method of claim 1 , wherein the individual is heterozygous or homozygous for a N370S mutation in a gene encoding glucocerebrosidase.
4. The method of claim 1 , wherein the individual is heterozygous for a R496H mutation in a gene encoding glucocerebrosidase.
5. The method of claim 1 , wherein the individual is heterozygous or homozygous for a L444P mutation in a gene encoding glucocerebrosidase.
6. The method of claim 1 , wherein the individual has a mutation in a gene encoding β-glucocerebrosidase.
7. The method of claim 1 , wherein the individual is heterozygous for an 84GG mutation.