Methods to treat neurological diseases

Patent metadata

Field	Value
Publication number	US-10758545-B2
Application number	US-201615579546-A
Country	US
Kind code	B2
Filing date	Jun 24, 2016
Priority date	Jun 25, 2015
Publication date	Sep 1, 2020
Grant date	Sep 1, 2020

Abstract

Disclosed is a method of treating a subject who has a neurological disease. The neurological disease may be associated with altered C9ORF72 protein activity. In one aspect, the method includes a step of administering an effective dose of a pharmaceutical composition to a subject in need thereof, thereby rescuing the defects associated with altered C9ORF72 protein activity. Also described are methods for identifying a compound for inhibiting motor neuron degeneration.

First claim

The invention claimed is:

1. A method of treating a subject having amyotrophic lateral sclerosis or frontotemporal dementia, comprising:
administering to the subject an effective dose of a PIKFYVE kinase inhibitor selected from the croup consisting of apilimod and YM201636,
wherein the treatment results in an alleviation, reduction, amelioration or improvement in the subject's condition,
and wherein the subject has reduced C9ORF72 gene activity.

2. The method of claim 1 , wherein the subject's C9ORF72 gene comprises a (GGGGCC) n repeat expansion located between exons 1a and 1b of the C9ORF72 gene, wherein n is an integer greater than 25.

3. The method of claim 2 , wherein the subject is haploinsufficient for the C9ORF72 gene.

4. The method of claim 3 , wherein the haploinsufficiency results in a 50% or greater reduction in C9ORF72 protein activity.

5. The method of claim 2 , wherein the C9ORF72 gene product comprises a dipeptide repeat resulting from the (GGGGCC) n expansion.

6. The method of claim 5 , wherein the dipeptide repeat is cytotoxic.

7. The method of claim 2 , wherein the expansion is a gain-of-function or loss-of function mutation.

8. The method of claim 1 , wherein the amyotrophic lateral sclerosis or frontotemporal dementia are associated with neuronal hyperexcitability.

Assignees

• Univ Southern California

Inventors

• Ichida Justin
• Lin Shaoyu
• Li Yichen
• Shi Yingxiao

Classifications

• C12N2310/20

  involving clustered regularly interspaced short palindromic repeats [CRISPR] · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61K31/5377 Primary

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• A61K31/27

  of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title