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066 Haptoglobin Treatment to Reduce Complications of Sickle Cell Disease

NHLBI SBIR/STTR Contract Topic

(Fast-Track proposals will be accepted)

Number of anticipated awards: 1-2

The release of hemoglobin into the circulation contributes to morbidity and mortality in intense hemolytic states such as sickle cell disease (SCD). Free hemoglobin related vascular reactivity, potentially through nitric oxide scavenging and oxidative stress associated with the iron moiety of heme likely result in pulmonary arterial hypertension, stroke and the acute chest syndrome in SCD. A glucocorticoid induced increase in haptoglobin synthesis in animal models has demonstrated an attenuation of the adverse clinical effects of free hemoglobin. (J Clin Invest [2009] 119:2271-80)

In SBIR Phase I, offerors are requested to establish a technical and scientific approach and demonstrate the feasibility of manufacturing a human plasma derived haptoglobin concentrate that is representative of the known human polymorphisms. The haptoglobin concentrate would be produced from plasma fractionation using established methodologies (such as Cohn or Kistler/Nitschmann methods) that could support scale-up in production to clinically relevant quantities.

The hypothesis to be tested in SBIR Phase II studies is that well-characterized, infused haptoglobin would complex with free hemoglobin and accelerate its clearance by CD163 on macrophages. This clearance should reduce the risk of altered vascular reactivity due to nitric oxide binding and similarly, reduce oxidative tissue damage mediated by heme iron. These possible effects will be tested in SBIR Phase II studies including a dose escalation safety study in human volunteers including determination of biomarkers which, if successful, could be followed by a trial to examine a dose response for painful events and/or the acute chest syndrome as clinical endpoints in individuals with SCD.

For more information, contact OTAC.

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Last Updated December 2011

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