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Brain penetrant Hsp90 inhibitors for Alzheimer's disease

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R42AG042205-02
Agency Tracking Number: R42AG042205
Amount: $1,473,584.00
Phase: Phase II
Program: STTR
Solicitation Topic Code: NIA
Solicitation Number: PA13-235
Solicitation Year: 2014
Award Year: 2014
Award Start Date (Proposal Award Date): 2014-09-01
Award End Date (Contract End Date): 2016-06-30
Small Business Information
1770 Massachusetts Avenue, Suite 170
Cambridge, MA 02140-2808
United States
DUNS: 831491571
HUBZone Owned: No
Woman Owned: Yes
Socially and Economically Disadvantaged: No
Principal Investigator
 (617) 953-4618
Business Contact
Phone: (617) 953-4618
Research Institution
BOSTON, MA 02115-6110
United States

 Domestic nonprofit research organization

DESCRIPTION provided by applicant Neurodegeneration in Alzheimerandapos s disease AD may result from deposition of A as plaques in brain tissue However less effort has been made to elucidate the role of tau containing neurofibrillary tangles NFTs in AD Accumulating evidence suggests that tau containing NFTs is an important component in the initiation and progression of AD and other neurodegenerative diseases In this proposal the tau pathway is targeted through inhibition of the molecular chaperone heat shock protein Hsp as a promising new approach to affect the disease progression of AD This proposal builds on the specific aims set forth and achieved under the STTR Phase I funding a to conduct structure activity relationship studies to obtain brain permeable Hsp inhibitors and b to evaluate biochemical and cellular Hsp inhibition These efforts yielded novel proprietary Hsp inhibitors with acceptable drug like properties including good brain concentration Since the conclusion of Phase I funding Yuma Therapeutics has generated pharmacokinetic data in mice for an early lead compound YT further supporting its drug like properties The proposed studies for Phase II focus on a evaluating our lead compound in an in vivo transgenic mouse model of tauopathy on the levels of total tau and phosphorylated tau in cerebrospinal fluid tau neuropathology and behavioral outcomes b manufacturing scale up of active pharmaceutical ingredient API of a lead candidate and initiate in vivo toxicology studies and c formulation work on the API PUBLIC HEALTH RELEVANCE This research is focused on identifying potential drug candidates to treat Alzheimerandapos s disease AD and in this way it addresses NIAandapos s priorities to support research on health and disease in the aged Furthermore this project targets the tau pathway as a promising new approach to affect the disease progression of AD

* Information listed above is at the time of submission. *

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