SBIR-STTR Award

Hemex, Inc. has developed a hollow fiber device with immobilized chelators for the extracorporeal removal of toxic metals from blood, specifically aluminum (Al). This device, similar to a hemodialysis cartridge, is a novel approach to detoxification, with unique advantages over existing treatments: (1) the immobilized chelator does not enter the blood, minimizing the danger of toxicity; 12) the device functions with efficiency due to the large concentration of chelator and extensive contact area and is specific toward a given metal according to the chelator used; and (3) blood compatibility of the hollow fibers assures safety of application. The safety and efficacy of the proposed device are particularly attractive as the current chelator therapy of Al intoxication has potential toxicity.In Phase I, Hemex, Inc. plans to finalize design of the device by selecting specific chelators for Al and testing their efficacy in vitro, using blood from patients with Al intoxication. The most effective device will be further evaluated in Phase II in experimental animals to assure in vivo efficacy and safety. The development of the optimal device will lead to an Investigational Device Exemption lIDE) and clinical testing in patients on chronic hemodialysis.National Heart, Lung, and Blood Institute (NHLBI)

Desferrioxamine (DFO) given intravenously for treatment of aluminum (Al) intoxication is highly toxic itself. To bypass toxicity, Hemex, Inc., has immobilized DFO into a hollow-fiber device for the extracorporeal removal of Al from blood. Such a device, similar to a hemodialysis cartridge, is a novel approach to detoxification with unique advantages: (1) the immobilized chelator does not enter the blood, so toxicity is minimized; (2) the device is highly efficient due to a large contact area with high concentrations of chelator, and specific toward a given metal according to the chelator used; and (3) blood compatibility of hollow fibers assures safety of application.In Phase I, Hemex, Inc., prepared and tested four DFO conjugates and two commercial resins immobilized into hollow-fiber cartridges. When tested with recirculating Al solutions and patients' blood, the degree of Al removal was of clinical significance. In Phase II, three DFO conjugates will be immobilized into the chelator device and tested for Al uptake using recirculating saline. Blood from dialysis patients will be recirculated through chelator devices to examine if the amount ofultrafilterable Al increases during the experiment, at the expense of the protein-bound fraction. The steps in manufacturing will be streamlined. The best-performing chelator device will be developed as a prototype and will be tested in animals for safety of in vivo application.

Anticipated Results:
Severe Al toxicity occurs in 30 percent of the 104,000 patients currently treated with dialysis. Parenteral DFO is too toxic for chronic application. Thus, about 35,000 patients may benefit from a chelator device. The device will be applied simultaneously in series with hemodialysis. Pending success in future clinical trials, partnership interest for commercial development has been expressed by two companies.National Heart, Lung, And Blood Institute (NHLBI)