INHIBITORS OF A GLIAL ANTIPROIFERATIVE FACTOR

EACH YEAR 300,000 PEOPLE IN THE UNITED STATES SUFFER DAMAGE TO PERIPHERAL NERVES. OF THE 50,000 OPERATIONS PERFORMED, 50% OR LESS ARE SUCCESSFUL. GLIATECH, INC. IS DEVELOPING AN ARTIFICIAL NERVE GRAFT SEEDED WITH SCHWANN CELLS. THE CURRENT PROTOCOL CALLS FOR REMOVING A SEGMENT OF NERVE FROM A PATIENT PURIFYING AND EXPANDING THE SCHWANN CELLS AND REINTRODUCING THESE CELLS INTO THE PATIENT AS AN ARTIFICIAL NERVE GRAFT. THE PROCESS NOW TAKES UPWARDS OF 6 WEEKS. RECENT STUDIES HAVE INDICATED THAT A SPECIFIC PROTEASE PRODUCED BY SCHWANN CELLS (SCP) LIMITS THEIR PROLIFERATION EVEN IN THE PRESENCE OF POTENT MITOGENS THIS PROJECT IS AIMED AT SHORTENING THE TIME NEEDED FOR THE SCHWANN CELLS TO PROLIFERATE, THUS IMPROVING THE PRODUCT PERFORMANCE. IN THIS RESEARCH, WE WILL IDENTIFY PROTEASE INHIBITORS WHICH SPECIFICALLY ANTAGONIZE SCP, THEREBY ENHANCING THE PROLIFERATION OF SCHWANN CELLS IN VITRO AND REDUCING THE TIME NEEDED TO EXPAND THE CELLS. IN PHASE I THE EFFECT OF ADDING SPECIFIC PROTEASE INHIBITORS ON THE PROLIFERATION OF SCHWANN CELLS WILL BE DETERMINED IN VITRO. IN PHASE II, THIS WOULD BE EXPANDED BY TESTING IN AN IN VIVO MODEL THE EFFICACY OF SPECIFIC INHIBITORS INCORPORATED INTO AN ARTIFICIAL NERVE GRAFT.