Goal 3: Advance Translational Research

Development of Novel Apheresis Adsorption Technologies to More Effectively and Safely Treat Hematologic Diseases

Current FDA approved apheresis technology currently uses elutriation/centrifugation separation techniques to remove pathologic cellular and/or plasma elements. These techniques are non-specific, limited by inefficient removal kinetics and often require considerable blood product exposure. Despite tremendous improvement in our understanding of the pathophysiology of a variety of disease, our ability to treat many of diseases using apheresis has not changed since the development of the modern cell separator in the 1980s. Development of novel apheresis technologies are needed to selectively remove pathologic cellular and/or plasma elements to improve current treatment modalities and/or provide novel treatment approaches in these patients.

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Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

More efficient and novel means of selectively removing pathologic cellular and/or plasma elements are needed when a disease specific pathologic cellular element or plasma element is identified (i.e. anti-RBC autoantibodies in patient with severe autoimmune hemolytic anemia, anti-platelet antibody in patients with autoimmune thrombocytopenic purpura, anti-platelet factor four antibodies associated with heparin associated thrombocytopenia, complement fixing, donor specific antibodies in antibody mediated cardiac rejection, antibodies implicated in catastrophic antiphospholipid syndrome, mediators of the inflammatory response in sepsis, etc. ).

 

These are especially needed in patients who are critically ill and in need of rapid removal of these pathologic blood elements. Selectively and rapidly removing disease associated cellular and/or plasma elements while returning the remainder of the patient’s cells and/or plasma can minimize additional blood product exposure with its attendant risks, reduce duration of treatment significantly, and offer new forms of treatment either not available in the U.S. or not previously considered.

Feasibility and challenges of addressing this CQ or CC :

Selective removal of pathologic plasma elements has been demonstrated by the development of selective adsorption columns which bind inflammatory mediators and immunoglobulins, but are not currently being used in the U.S. Current technology exists to remove specific pathologic plasma elements. For example, immunoadsorption technology, which incorporates polyclonal sheep anti-human IgG antibodies bound covalently to sepharose columns can remove >98% of all IgG subclasses after multiple treatment sessions. Similar effect can be obtained by Protein A sepharose column (Prosorba) technology which had been approved for use by the FDA for rheumatoid arthritis; however, in 2006 the manufacturer stopped producing the column due to financial reasons. Clearly, research into the use of these columns in the context of well designed, randomized clinical trials would be readily feasible with the appropriate IND and require industry support.

 

Furthermore, the technology that is used to couple sheep anti-human IgG antibodies to sepharose, can used to create antigen specific adsorption columns for removal of specific pathologic antibodies, for example, anti-PF4 antibodies that are involved in heparin associated thrombocytopenia, or Clq dependent (C1q) donor specific HLA antibodies that are involved in antibody mediated cardiac rejection. Industry support/small business grant support will be needed for development of these columns in addition to clinical trials demonstrating efficacy

Name of idea submitter and other team members who worked on this idea : Edward Wong on behalf of ASFA

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Idea No. 657