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A Novel Insulin Pathway Agonist for Alzheimer's Disease

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AG044871-01
Agency Tracking Number: R41AG044871
Amount: $147,729.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIA
Solicitation Number: PA12-089
Solicitation Year: 2013
Award Year: 2013
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
99 Hayden Ave, STE210
LEXINGTON, MA 02421-7965
United States
DUNS: 786461967
HUBZone Owned: No
Woman Owned: Yes
Socially and Economically Disadvantaged: No
Principal Investigator
 (781) 396-0476
Business Contact
Phone: (781) 676-2000
Research Institution
PROVIDENCE, RI 02903-4923
United States

 () -
 Domestic Nonprofit Research Organization

DESCRIPTION (provided by applicant): Even though the association of -amyloid peptide (A ) deposition and Alzheimer's Disease (AD) underpins the major hypothesis for disease progression and possibly causation and several drugs addressing the formation or removal of -amyloid plaques have entered clinical trials, no effective therapy exists to date for AD. This reality calls for new targets that are not based on -amyloid supply side or removal but address its toxic effects on critical neuronal survival, metabolic and plasticity pathways. There is widening recognition that AD is an insulin resistant state affecting the brain, a so-called 'type II diabetes' In our studies, we have found a potential novel therapy to both restore insulin sensitivity and hasten Aremoval. We found literature precedence for an unnamed allosteric activator of the kinase PDK-1 (CAS 1180676-32-7 or PS48), a chlorophenyl pentenoic acid. When tested in cultured cells and cell-free systems, PS48 was found to be reverse the negative amyloid effect by restoring Akt activation. We propose to use its structure and activity as a scaffold for the discovery of additional like-acting compounds. In this way several small libraries based on PS48 will be prepared and tested to try and optimize thetherapeutic effect and other pharmacologic properties of this lead compound. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: The goal of this Phase I proposal is to develop lead pre-clinical compounds which restore normal insulin pathway function in individuals with sporadic Alzheimer's Disease (AD). There is significant evidence for dysregulation of the insulin pathway in AD. In our studies, we have found a potential novel therapy to restore insulin sensitivity and hasten A removal.

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

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