Version 2.1.1.0

Abstract

Grant Number:	1R43AG023457-01
PI Name:	SUNDARAM, PAZHANI
PI Email:	reply@recombtech.com
PI Title:
Project Title:	Detoxification Depot for Beta-amyloid peptides

Abstract: DESCRIPTION (provided by applicant): The long-term goal is to develop an effective therapy for Alzheimer's disease, by using a subcutaneous hydrogel to recognize, concentrate and eliminate beta-amyloid (Abeta) peptides and thereby halt deposition of plaque in the brain. The hydrogel forms in situ from an injected solution within about 1 minute after mixing nucleophile-modified poly (ethylene glycol) (PEG) with electrophile-modified cross-linker in the presence of the Abeta binding element. The hydrogel will slowly and steadily accumulate ABeta, acting as a "sink" to draw these toxic peptides across the blood-brain barrier. This sink effect is based on the strong and specific binding provided by aggregates of the retro-inverso peptide (RIP), phe-phe-val-leu-lys, which will be covalently linked to PEG chains in the hydrogel. We already have developed the hydrogel as a drug delivery system and we have proven the capability of the RIP to bind target Abeta. The current proposal is a logic application of our previous research to develop a "detoxification depot" that may eventually help control and or cure Alzheimer's disease. The goal of Phase I is to establish proof-of-principle that we can use the hydrogel as a detoxification depot in vitro. Phase II will concern applying this depot to lowering the concentration of Abeta using an experimental mouse model, in vivo. The final goal will be inhibition of plaque deposition in the mouse model.

Thesaurus Terms:
Alzheimer's disease, amyloid protein, detoxification, peptide, technology /technique development
blood brain barrier, drug delivery system, gel, neuritic plaque, protein binding, synthetic peptide
disease /disorder model, ethylene glycol

Institution:	RECOMBINANT TECHNOLOGIES, LLC
	25 SCIENCE PARK, STE 298, BOX 7
	NEW HAVEN, CT 06511
Fiscal Year:	2003
Department:
Project Start:	30-SEP-2003
Project End:	31-MAY-2004
ICD:	NATIONAL INSTITUTE ON AGING
IRG:	ZRG1

---