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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)


Relevant Publication:
  1. 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


Ref No: 2076

Updated: 02/2011

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