Research Project
2223849
The magnitude of lead intoxication in our country and the problem with its treatment have created a medical emergency; treatment requires hospitalization, available chelators have serious side effects, and cost of using them is astronomical. We have developed a novel approach to detoxification, a device with immobilized chelators, for extracorporeal removal of lead from blood and storage sites. Since the chelator is immobilized, chelation occurs outside the circulation and toxicity of chelation is eliminated. A prototype of such a device, an enzyme reactor, was clinically safe and effective. With Phase I support we determined, that it is feasible to develop a lead- chelating device which removes clinically significant amounts of lead. Of several chelators tested dithiocarbamate derivatives had the greatest capacity and specificity; when immobilized in device, they removed over 90% of lead added to circulating solutions or to serum. With Phase II support we plan to continue manufacturing modifications in order to produce a prototype lead chelating device for clinical use: with adequate capacity, lead selectivity and moderate cost. The potential prototype will be tested in dogs with chronic lead intoxication for safety and lead removing capacity. Results of the studies will become part of the FDA application for clinical testing. Lead detoxification with chelator device will be a 2-3 hr outpatient procedure instead of a week-long hospitalization. It will be more convenient to the patient, much less costly, and safe enough for treating pregnant women.
