# US 10,864,206 B2 · Treatment of neurodegenerative conditions by disruption of Rhes

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- Number: US 10,864,206 B2
- Document ID: US10864206B2
- Status: Granted
- Kind: B2
- Application number: 16/162,239
- Filed: 2018-10-16
- Published: 2019-03-21
- Granted: 2020-12-15
- Earliest claimed: 2017-01-16
- Assignees: The Regents of the University of California
- Applicants: The Regents of the University of California
- Inventors: Kenneth Kosik; Israel Hernandez
- Web page: https://patentgrep.com/patent/US10864206B2

## CPC

- A61K 31/4545: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
- A61K 31/12: Ketones
- A61K 31/223: of alpha-aminoacids
- A61K 31/4709: Non-condensed quinolines and containing further heterocyclic rings
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/28: 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
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention is directed to the treatment of tauopathic neurodegenerative conditions and the underlying processes thereof. Based on the discovery that Rhes acts as a negative regulator of normal tau clearance, the compositions and methods of the invention may be applied to inhibit Rhes and reduce pathogenic tau aggregation. Rhes may be disrupted by disrupting RAS2D gene expression or reducing the abundance of Rhes protein in neurons. Additionally, post-translational modifications of Rhes may be targeted, including the disruption of Rhes farnesylation by the administration of farnesyltransferase inhibitors.

## Claims

### Claim 1

A method of treating a tauopathy in a subject, comprising
administering to the subject a pharmaceutical composition comprising a farnesyltransferase inhibitor;
wherein the tauopathy is selected from the group consisting of corticobasal degeneration, argyrophilic grain disease, chronic traumatic encephalopathy, Niemann-Pick-C, Guam-AL S-Parkinson's-dementia, post-encephalitic Parkinson's disease, Subacute sclerosing panencephalitis, and progressive supranuclear palsy.

### Claim 2 (depends on 1)

The method of claim 1, wherein
the farnesyltransferase inhibitor is selected from the group consisting of: lonafarnib, tipifarnib, gingerol, gliotoxin, α-hydroxy farnesyl phosphonic acid, manumycin A, chaetomellic acid A, clavaric acid, FPT Inhibitor I, FPT Inhibitor II, FPT Inhibitor III, FTase Inhibitor I, FTase Inhibitor II, FTI-276 trifluoroacetate salt, GGTI-297, FTI-277 trifluoroacetate salt, and L-744,832 dihydrochloride.