ISLET GRAFTS IN SERTOLI CELL IMMUNOPRIVILEGED SITES

Type I diabetes and its complications is a tremendous cost to the health care system. Implementing islet transplantation to enable patients to regain physiological control of their blood glucose levels faces two major obstacles: lack of human donor pancreases and graft rejection. Use of animal cells or tissues and immunosuppression could ameliorate these problems, but introduce additional problems, particularly chronic administration of toxic immunosuppressive agents. Sertoli Technologies, Inc. is developing a diabetes cellular therapy and product based on Sertoli cell and islet xenografts that provides limited and localized, not systemic, immunosuppression and enhanced growth of engrafted tissue. The proposed development systematically builds on our initial experience with our chosen Sertoli cell and islet source, establishes quality criteria for the cells, demonstrates the efficacy of the therapy in chemically-induced and autoimmune diabetic rodents, explores immunosuppression options, transplant sites and the effect of pretolerization and estimates a cell dose-response relationship. These data will establish our commercial product, satisfy regulatory concerns and enable future safety and efficacy studies in higher animals as a prelude to initiation of xenotransplantation in type I diabetic patients. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 267 --PROJECT NUMBER......1 R43 DK52723-01 INVESTIGATOR NAME/ADDRESS FY 97 KLEIN, PETER D IRG/INTRAMURAL UNIT..ZRG3 MERETEK DIAGNOSTICS, INC AWARD AMOUNT......... $90,207 1709 DRYDEN RD, SUITE 1513 HOUSTON, TX 77030 PERFORMING ORGANIZATION: MERETEK DIAGNOSTICS, INC. TITLE NEW 13C PROBE OF SOLID AND LIQUID PHASE GASTRIC EMPTYING ABSTRACT: Conventional measurements of gastric emptying (1) employ radioactive tracers, (2) require preparation of the liquid and solid phases of the meal immediately before the test, and (3) require a gamma scintillation camera to record the passage of the labeled meal from the stomach. We have developed a breath test kit containing a meal suitable for measurement of gastric emptying in a physician's office. The 340-calorie meal contains 90 g solid phase and 90 g liquid phase, either of which may be labeled with a proprietary 13C tracer. The meal is palatable, as well as stable for at least a week at room temperature and for several months when frozen. Conduct of the measurement requires only that the subject consume the meal and collect five breath samples. Preliminary validation against radioactive measurements indicates excellent correlation and suggests the test can be carried out within 120 minutes. Phase I of this SBIR proposes individual validations against solid and liquid radioactive measures in 10 normal subjects and 30 patients with gastric dumping or paresis. In Phase II, multicenter clinical trials will be carried out to provide the basis for a 51OK submission to the Food and Drug Administration.