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Development of a Novel Therapeutic for Alzheimer' Disease

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
Program Year/Program:
2012 / STTR
Agency Tracking Number:
R41AG044187
Solicitation Year:
2012
Solicitation Topic Code:
NIA
Solicitation Number:
OD12-004
Small Business Information
COPLEX THERAPEUTICS, LLC
404 CLYDEBANK COURT LOUISVILLE, KY 40243-
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2012
Title: Development of a Novel Therapeutic for Alzheimer' Disease
Agency: HHS
Contract: 1R41AG044187-01
Award Amount: $99,973.00
 

Abstract:

DESCRIPTION (provided by applicant): Traditional approaches to drug development for Alzheimer's disease are becoming increasingly expensive and in many cases disappointingly unsuccessful. Based on preliminary in vitro and in vivo studies we have identifieda novel lactam derivative of the commonly prescribed 1,4 dihydropyridine calcium channel blocker nifedipine (1-acetyl-2,4- dimethylbenzo[c][2,7]naphthyridin-5(6H)-one; NFD-L) that lacks calcium channel blocking capacity but significantly decreases Ass1-42production by increasing levels of alpha-secretase (ADAM-10) and decreasing levels of presenilin-1 and nicastrin (components of the gamma secretase complex). Based on our preliminary data, the hypothesis to be tested in this proposal is that NFD-L lacks calcium channel blocking capacity and potential adverse cardiovascular side effects, effectively diminishes generation of A?1-42 by increasing levels of alpha-secretase (ADAM-10) processing of APP and by decreasing levels of proteins involved in A?1-42 processing (presenilin-1 and nicastrin), and improves spatial learning in a mouse model of amyloid deposition. In addition, we hypothesize that NFD-L does not lead to microhemorrhages or edema (amyloid related imaging abnormalities; ARIA) that are associated with immunotherapy mediated A? clearance. If successful, the data obtained in this proposal would further clarify the effects of NFD-L on A? processing and confirm whether or not it induces ARIA which would address FDA concerns and potentially increase thelikelihood of successful commercialization of NFD-L. PUBLIC HEALTH RELEVANCE: Currently two classes of medications are FDA approved for use by Alzheimer's disease (AD) patients including cholinesterase inhibitors (Aricept) and an N-methyl-D-aspartate (NMDA) antagonist (Memantine). Although these therapeutics show clinical benefit in some patients, many do not respond. Additionally, these drugs do not significantly modify disease progression and perhaps more importantly are not approved for patientsat earlier stages of the disease (mild cognitive impairment; MCI). For these reasons there is a critical need to identify additional therapeutics that can be initiated early in the disease progression to alter the pathogenesis of the disease. Preliminaryand future studies described in this proposal aim to test the efficacy of a novel derivative of a commonly prescribed calcium channel blocker in a mouse model of amyloid beta (A 1-42) deposition (APP/PS1 mice) and to determine if the novel therapeutic leads to microhemorrhages or edema as has been observed in studies using A immunotherapy. If successful, the results of the proposed studies would address concerns that have been raised by the FDA regarding amyloid lowering agents and further support testingof the compound in clinical trials.

Principal Investigator:

Mark A. Lovell
859-257-1412
malove2@uky.edu

Business Contact:

John Beran
502-767-1020
jeberan@insightbb.com
Small Business Information at Submission:

COPLEX THERAPEUTICS, LLC
404 CLYDEBANK COURT LOUISVILLE, KY 40243-

EIN/Tax ID: 126271411
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
Research Institution Information:
UNIVERSITY OF KENTUCKY
UNIVERSITY OF KENTUCKY
109 KINKEAD HALL
LEXINGTON, KY 40506-0057
Contact: