Novel Neuropeptides as Targets for Psychiatric Disorders

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$500,000.00
Award Year:
2004
Program:
SBIR
Phase:
Phase I
Contract:
1R43MH072162-01
Award Id:
71748
Agency Tracking Number:
MH072162
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
AFASCI, INC., 2633 MARTINEZ DR, BURLINGAME, CA, 94010
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
n/a
Principal Investigator:
XINMINXIE
(650) 692-6051
simonxie@afasci.com
Business Contact:
XINMINXIE
(415) 338-3334
SIMONXXIE@HOTMAIL.COM
Research Institute:
n/a
Abstract
DESCRIPTION (provided by applicant): Agents acting at G-protein coupled receptors (GPCRs) have been the most successful targets for drug development. Every new GPCR identified is immediately examined for their potential clinical applications. Likewise all novel endogenous neuropeptides are viewed as the key to discovering and unlocking the actions of an orphan GPCR. Neuropeptides are particularly important because of their proven involvement in stress, anxiety and depression, thus providing new targets for the unmet medical needs in psychiatric disorders. The identification of novel neuropeptides that act as the endogenous ligand for orphan GPCRs has been a slow and costly process that required the purification of an unstable peptide from a brain homogenate. This process has been dramatically improved by using our newly developed computational methodology. Several putative prohormones based on species comparison and pattern recognition have been identified from either the Celera Discovery System (CDS) or public sources (GenBank). In this Phase I project, first we will confirm the existence of prohormones by identifying there transcripts using quantitative rtPCR and localizing their expression using in situ hybridization and Northern blots. Antibodies to the neuropeptide will be produced and used for verification of the presence of the endogenous peptide. Secondly we will characterize the novel neuropeptides for in vitro binding and electrophysiological activity in mouse brain slices. Finally, a battery of standard neurobehavioral tests will be conducted to identify the functional significance of the novel neuropeptides in vivo. The novel peptides will serve as a basis for the discovery and development of small-molecule mimetics. These studies will be carried out in the Phase II (to be proposed later), in which the GPCR for the peptides will be identified and small molecule agonists and antagonists will be developed. Our ultimate goal is to develop new therapeutics for indications in anxiety, depression, schizophrenia, or other pathological symptoms often modulated by the endogenous neuropeptide system.

* information listed above is at the time of submission.

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