Research Project
6152994
Stroke is the greatest cause of severe disability in western countries. Recently, one thrombolytic therapy has been approved for acute stroke-- rtPA. This treatment must be administered within 3 hours of stroke onset, limiting its general usefulness. The long term objective of the research in this proposal is to develop sCRl sLex to be used alone or in combination with thrombolytics to increase the dosing time window and reduce neurological damage. This novel glycoprotein has two anti-inflammatory activities: l) it inhibits complement activation; 2) it is a selectin ligand. The anti-inflammatory properties of this molecule should act to prevent further neurological damage from both ischemia and the reperfusion induced by thrombolytics. We have demonstrated preclinical efficacy of this molecule ill a recent publication . The sLex moiety that provides the anti-selectin function provides a unique challenge in the production of this glycoprotein. The immediate goal of this proposal is to develop a scaleable method to consistently produce this molecule with the requisite oligosaccharides and to preserve the production cell line. This will be performed by adapting the cell line to suspension culture and by optimizing the current medium and culture conditions. The development of a commercializable GMP process is required before this product can move forward into clinical testing. Successful clinical development of this complement inhibitor and selectin ligand will greatly add to the ability to treat the neurological damage induced acutely in stroke. Any therapy that can limit the single largest cause of disability-in this country should have great impact on reducing the cost of long tend care. PROPOSED COMMERCIAL APPLICATION: There are 600,000 cases of stroke in the U.S. each year. Stroke is the third leading cause of death and the leading cause of disability. A beneficial therapy, which could be administered prior to diagnostic screening for the type of stroke, would address this large market. sCRlsLex also has the potential to address other large markets for indications involving selectins and complement including head trauma, myocardial infarct, cardiac surgery, and transplantation.
