Drug discovery of anti-ADDL therapeutics for Alzheimer's

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R43AG026951-01
Agency Tracking Number: AG026951
Amount: $183,750.00
Phase: Phase I
Program: SBIR
Awards Year: 2005
Solitcitation Year: 2005
Solitcitation Topic Code: N/A
Solitcitation Number: PHS2005-2
Small Business Information
Acumen Pharmaceuticals, Inc., 385 Oyster Point Blvd., South San Francisco, CA, 94080
Duns: N/A
Hubzone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (847) 417-6538
Business Contact
Phone: (650) 875-7700
Research Institution
DESCRIPTION (provided by applicant): Recent evidence suggests that the primary cause of Alzheimer's disease is the progressive accumulation of neurotpxic oligomeric assemblies of the Abeta 1-42 protein. These neurotoxic oligomeric species are known as ADDLs (Ab-derived diffusible ligands). In Tg2576 AD mice, a transgenic Alzheimer's disease animal model, memory performance declines as ADDL levels increase. Human patients with Alzheimer's disease show a 70-fold elevation in ADDL levels relative to unaffected age-matched controls. ADDLs affect memory by directly interfering with synaptic function, which eventually results in synaptic loss over time. This evidence suggests that small molecule, ADDL-directed therapeutics might prevent ADDL-induced cognitive deficits, and slow or reverse disease progression in humans. This stands in contrast to current FDA-approved drugs, which treat the symptoms and not the underlying cause of Alzheimer's disease. The most promising approach to ADDL-directed therapeutics is to prevent ADDL formation by blocking assembly of the Abeta 1-42 protein. The subject of this proposal is to establish and validate a cascade of primary and secondary chemical screens and screen a representative CNS targeted chemical library to identify small molecules that block ADDL assembly. In Phase I, we propose to develop and validate a homogeneous ADDL assembly blocker screening assay, conduct molecular dynamics simulations to build an ADDL structural model, and carry out pilot screening of a selected small molecule library.

* information listed above is at the time of submission.

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