Novel Methods for Dissolving Blood Clots

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R41HL092750-01A2
Agency Tracking Number: R41HL092750
Amount: $167,685.00
Phase: Phase I
Program: STTR
Awards Year: 2010
Solitcitation Year: 2010
Solitcitation Topic Code: NHLBI
Solitcitation Number: PHS2010-2
Small Business Information
UNIVERSITY OF TENNESSEE HEALTH SCI CTR
1840 Overton Park Avenue, Memphis, TN, -
Duns: 803592364
Hubzone Owned: N
Woman Owned: Y
Socially and Economically Disadvantaged: N
Principal Investigator
 GUY REED
 (617) 432-4992
 glreed@translationalsciences.com
Business Contact
 ELIXABETH REED
Phone: (901) 448-5571
Email: dsmith@uthsc.edu
Research Institution
 University Of Tennessee Health Sci Ctr
 62 S Dunlap, Suite 300
MEMPHIS, TN, 38163-
 () -
 Nonprofit college or university
Abstract
DESCRIPTION (provided by applicant): Cardiovascular disease is the leading cause of death worldwide. Current therapies for cardiovascular disease are associated with partial success, restricted access, delays, possible neurotoxicity and other important limitations. Our goal is to develop a novel therapeutic agent that is safer and more effective at dissolving the blood clots (thrombi) that cause heart attacks and strokes. Studies of humans and mice with lifelong deficiency of a2-antiplasmin (a2AP) have shown that it is the major regulator of blood clot dissolution. We have produced high affinity monoclonal antibodies that induce functional a2AP deficiency. We have shown that these monoclonal antibodies cause venous thrombi and pulmonary emboli to dissolve in vivo. They also accelerate the dissolution of cerebral arterial thrombi-thereby reducing stroke size without increasing bleeding. In this Phase I application, we will modify these promising antibodies by molecular engineering techniques to convert them into potential therapeutics suitable for human trials. In Aim 1 we will engineer and express a chimerized antibody and antibody fragment (Fab). In Aim 2 we will evaluate the relative abilities of the antibody and antibody fragment to bind and inhibit a2AP and enhance blood clot dissolution. With successful completion of these aims we will pursue a Phase II application to optimize the production of these molecules in order to examine their safety and efficacy in suitable pre-clinical models. PUBLIC HEALTH RELEVANCE: Cardiovascular disease is the leading cause of death worldwide. Each year ~ 1.6 million Americans suffer a heart attack or stroke. The resulting death and disability costs the U.S. a staggering 316 billion a year. Current therapies are associated with partial success, restricted access, delays, possible neurotoxicity and other important limitations. This project seeks to develop a novel therapy for heart attacks and strokes that could markedly reduce death, disability and costs.

* information listed above is at the time of submission.

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