NEW AGENT FOR PREVENTION/TREATMENT OF UROLITHIASIS

Urolithiasis affects one million people annually in the United states; of these 354,000 require hospital admission. About 40% will experience a recurrence within five ears. the peak age of onset of the disease in both male and females is between 20 and 30 years. It frequently becomes a lifelong disorder requiring continued monitoring and treatment. The need for an effective treatment has prompted Costello Pharmaceutical to investigate an orally administered extract from the plan Eriobotrya japonica. In vivo studies using an animal model confirm it prevents calcium oxalate stone formation. The active moiety is a galacturonic acid containing cell wall polysaccharide. Proposed studies are locally sequenced to increase our knowledge of the extract and to provide a basis for proceeding to the next study. The studies will 1) isolate and purify the active moiety; 2) establish the chemical and structural composition of the active moiety and consequently the likelihood of synthesis and 3) prepare purified compound for future (Phase 2 SBIR) in vivo studies. The Complex Carbohydrate Research Center (CCRC) will provide guidance and assistance to us in the purification of the active moiety and will establish composition and structure of this compound at their research center. $ = 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 255 --PROJECT NUMBER......2 R44 DK49946-02 INVESTIGATOR NAME/ADDRESS FY 97 KLEIN, PETER D IRG/INTRAMURAL UNIT..ZRG3 MERETEK DIAGNOSTICS, INC AWARD AMOUNT......... $374,525 1709 DRYDEN RD, SUITE 1513 HOUSTON, TX 77030 PERFORMING ORGANIZATION: MERETEK DIAGNOSTICS, INC. TITLE DEVELOPMENT OF A NEW 13C AMINOPYRINE BREATH TEST KIT ABSTRACT: The aminopyrine breath test (ABT) is a noninvasive assay of hepatic mixed-function oxidase that correlates with the active hepatocyte volume. This measurement has potential diagnostic utility in assessing liver disease, alcohol and drug abuse, and in predicting the need for liver transplantation. The use of 13C-aminopyrine has been hampered by a lack of fully developed kits and analysis facilities. Phase I of this application covered the design and construction of a kit embodying new concepts in breath collection, storage, and analysis to make the 13C-ABT kit readily available to, and usable by, physicians. One thousand kits have been produced for use in multicenter evaluation trails in Phase II. Agreements to "piggyback" these trails on an existing 15 center cooperative study has been reached with 4 centers and other trail placements are being concluded. Clinical experience with the breath test will be used to obtain FDA 510K approval. In Phase III, an FDA-approved ABT kit will enable clincians to incorporate its use in the routine patient evaluation and management. The test kit will be marketed by Meretek Diagnostics, Inc., commerCIAL developers of the 13C-urea breath test for active Helicobacter pylori infection of the stomach. POTENTIAL COMMERCIAL APPLICATIONS Clinical validation of a 13C-aminopyrine breath test kit for 510K approval will provide clinicians with a valuable cost-effective diagnostic liver function test. $ = 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 256 --PROJECT NUMBER......2 R44 DK50737-02 INVESTIGATOR NAME/ADDRESS FY 97 BESCHORNER, WILLIAM E IRG/INTRAMURAL UNIT..ZRG2 XIMEREX, INC AWARD AMOUNT......... $402,414 4310 FARMFIELD COURT BALDWIN, MD 21013-9638 PERFORMING ORGANIZATION: XIMEREX, INC. TITLE SURROGATE TOLEROGENESIS IN XENOTRANSPLANTATION ABSTRACT: There is presently a severe and growing shortage of available human organ donors. Considerable interest has focused recently on the use of pigs as a potential source of transplant organs. Once hyperacute rejection was prevented, it became apparent that fulminant acute rejection is the major obstacle blocking the widespread use of pig organ xenografts. The severe immune suppression required to prevent this rejection would lead to an unacceptably high mortality rate. We have proposed a new approach to xenotransplantation, called "surrogate tolerogenesis" where tolerance is induced outside of the organ recipient, within the animal organ donor. This should greatly decrease the need for immune suppression. Initial phase I results using sheep as organ recipients, in fact, supported this proposition, where prolonged graft survival was achieved with only minimal suppression. Using large animal xenotransplant models, the proposed studies will further develop and evaluate surrogate tolerogenesis, in preparation for initial clinical studies of kidney transplants. The specific aims are to: 1. Evaluate potential improvements of surrogate tolerogenesis. 2. Assess the long term potential and complications of surrogate tolerogenesis. 3. Determine effectiveness in a discordant xenotransplant model. 4. Determine the cell populations essential for the transfer of tolerance back to the recipient.