Haptoglobin for Control of the Blood Pressure Response to Plasma Free Hemoglobin
Posted Feb 27 2011 7:00pm
Description of Invention: Release of hemoglobin into the blood is a central pathophysiologic event contributing to morbidity and mortality in chronic and acute hemolytic anemias and severe malaria. These toxicities arise from hemoglobin-related scavenging of nitric oxide, a blood vessel vasodilator, and peroxidative chain reactions that lead to damage of the surrounding tissues. Animal models have demonstrated both an attenuation of the hypertensive response due to nitric oxide scavenging and a prevention of peroxidative toxicity. Compartmentalization of hemoglobin, rather than short-lived nitric oxide-based drugs, may represent a new therapeutic paradigm in countering the pathophysiological side effects associated with free hemoglobin.
This technology identifies haptoglobin and haptoglobin mimetics as potential therapeutics for high blood pressure and intravascular toxicity due to release of hemoglobin from red blood cells. It provides a novel process in which free hemoglobin is compartmentalized within the haptoglobin molecule. Therapeutic proof-of-principle has been demonstrated for this technology in dog and guinea pig models.
Applications: A therapeutic for high blood pressure and intravascular toxicity resulting from free hemoglobin in the blood (as associated with hemolytic anemias such as sickle cell disease, paroxysmal nocturnal hemoglobinuria, and thalassemia, as well as cerebral malaria)
Advantages: Compartmentalization of hemoglobin may minimize toxicities associated with cell-free hemoglobin, in contrast to currently available nitric oxide-based drugs which seek to counterbalance but not minimize these toxicities.
Development Status: Pre-clinical stage
Inventors: Abdu I Alayash (FDA)
FS Boretti et al. Sequestration of extracellular hemoglobin within a haptoglobin complex decreases its hypertensive and oxidative effects in dogs and guinea pigs. J Clin Invest. 2009 Aug;119(8):2271-2280. [ PubMed: 19620788 ]
Licensing Status: Available for licensing.
Portfolios: Internal Medicine Internal Medicine - Therapeutics
For Licensing Information Please Contact: Fatima Sayyid MHPM NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325
Room 21, Rockville, MD 20852 United States Email: Fatima.Sayyid@nih.hhs.gov Phone: 301-435-4521 Fax: 301-402-0220