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Small molecule therapy for Alzheimer's disease

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
95684
Program Year/Program:
2010 / SBIR
Agency Tracking Number:
AG034712
Solicitation Year:
N/A
Solicitation Topic Code:
NIA
Solicitation Number:
N/A
Small Business Information
RECOMBINANT TECHNOLOGIES, LLC
RECOMBINANT TECHNOLOGIES, LLC 1090 MERIDEN WATERBURY TPKE CHESHIRE, CT 06410-7106
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2010
Title: Small molecule therapy for Alzheimer's disease
Agency: HHS
Contract: 1R43AG034712-01A1
Award Amount: $274,940.00
 

Abstract:

DESCRIPTION (provided by applicant): ABSTRACT The objective of our research is to develop an effective therapy for Alzheimer's disease (AD), by using an approach that is able to concentrate, bind and eliminate -amyloid peptides and thereby delay and or halt deposition of plaque in the brain. We have previously developed and demonstrated a detox gel system utilizing a retro-inverse peptide [ffvlk] to sequester A peptides, in vitro and in vivo. The current proposal is to explore and develop alterna te small molecules derived from diverse sources to capture A proteins. Therefore, we propose to synthesize different versions of new small molecules and examine their validity to bind A . We anticipate that these molecules are likely to exhibit similar or increased affinity for A based on recent preliminary data. Efficacy of the new compounds will be compared with the existing peptide by an in vitro model system developed in our laboratory. Following this, efficacy of the small molecules will be evaluated in AD model mice. The goal of this proposal is to establish proof- of-principle that alternate molecules can also be used to bind A thus increasing our catalog of potential drug candidates. The outcome of this research is the creation of a pipeline of a lternate therapeutic candidates to sequester toxic A peptides from the system. Development of alternate molecules becomes necessary as they can be used for a combination therapy, if needed. Besides, repertoire of candidate molecules will be useful to pick the ones with least side effects and toxicity in future studies. This study is expected to result in the identification of novel small molecules to treat AD. PUBLIC HEALTH RELEVANCE: In Alzheimer's disease (AD), complex extra cellular deposition o f -amyloid peptides (plaques) are formed in the brain. Plaques are mainly composed of A -40 and A -42 peptide aggregates. The ideal therapeutic should be able to disrupt this aggregation/deposition process. We have previously demonstrated that our hydrog el formulation with a retro-inverse (RI) peptide, f-f-v-l-k, sequesters A peptides in vitro and in vivo, which leads to decreased plaque formation. Administration of this gel in mice improved memory correlates. This RI peptide has its sequence derived fro m the residues 16-20 of the A peptide. We now propose to use a different set of small molecules derived from diverse sources as bait to capture the toxic A peptides. We propose to design these molecules in a way that they have decreased antigenicity /imm unogenicity and increased binding avidity to A . The long-term goal is to create a catalog of effective small molecule therapeutics and perform preclinical efficacy evaluation. The proposal is expected to result in the identification of new molecules with superior A binding characteristics.

Principal Investigator:

Pazhani Sundaram
2037871764
REPLY@RECOMBTECH.COM

Business Contact:

Paxhani Sundaram
reply@recombtech.com
Small Business Information at Submission:

RECOMBINANT TECHNOLOGIES, LLC
RECOMBINANT TECHNOLOGIES, LLC 1090 MERIDEN WATERBURY TPKE CHESHIRE, CT 06410

EIN/Tax ID: 106156252
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No