|YANG RESEARCH GROUP - ITP Bioreactor|
thrombocytopenic Purpura (ITP)
Immune thrombocytopenic purpura (ITP) develops as a result of enhanced platelet destruction through the interaction of auto-antibodies and platelet antigens. The prevalence of this disease is estimated at 5-6 per 100,000 individuals. Current methods of ITP treatment include coricosteroids (i.e. prednisone), intravenous immune globulin (IVIG), immunosuppressants, and splenectomy. While each of these methods are able, to certain extents, treat ITP, they also posses some inherent shortfalls. IVIG treatment, for example, provides short-lived effects while being very expensive and, in certain cases, creating some serious complications. Immunosuppressants put the patient at risk of opportunistic infections and splenectomy can be associated with a significant morbidity. Another method of treatment that is currently used is the PROSORBA column, which makes use of protein A immunoadsorption. This treatment method can also make an individual susceptible to opportunistic infections due to its non-specific removal of auto-antibodies.
Studies have shown that in ITP approximately 75% of the auto-antibodies are directed against platelet GPIIb/IIIa or GPIb/IX complexes. The goal of this project is to develop a hollow fiber based bioreactor for the specific removal of these auto-antibodies. Previously published results have shown that such a system has potential for ITP treatment. Briefly, hollow fiber reactors were developed using cellulose hollow fibers obtained from a dialysis cartridge. GPIIb/IIIa was then covalently attached to the lumen surface of the hollow fiber, and the reactor then utilized to treat rodents which had previously been dosed with 7E3 antibodies, as shown in the figure below.
With the promising preliminary results obtained, the project is now focused on improving the capacity, efficiency, and reproducibility of the ITP bioreactor. Since the hollow fibers provide a limited surface area for GPIIb/IIIa immobilization, we are looking to build layers of immobilized GPIIb/IIIa. Dr. Victor Yang likes to compare this with the building of skyscrapers in New York City ''when provided with a limited space to spread out, you must build up.'' To this end, we are making use of poly-lysine to ''build up'' the capacity of the bioreactors, see below. In addition, polyethylene glycol (PEG) molecules are used to provide greater mobility to the immobilized molecule.