LEPTIN AND HEMATOPOIESIS

DESCRIPTION: (Adapted from the Applicant's Abstract): The goal of this project is to develop therapeutic applications for leptin in treatment of hematopoietic diseases and transplantation. Recently they have found that leptin affects the survival and expansion of a population of bone marrow cells. A thorough characterization of the effect of leptin on fractionated bone marrow cells will be performed. The lineage of leptin specific target cells will be further delineated and the functional role of leptin in hematopoiesis will be investigated. Information obtained from this Phase 1 research will indicate the feasability of utilizing leptin as a therpeutic agent for the ex vivo expansion of trasnplantable progenitor cells and in vivo to accelerate recovery after transplantation. $ = 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 437 --PROJECT NUMBER......1 R43 HL59009-01 INVESTIGATOR NAME/ADDRESS FY 97 KLOSTER, KAIA L IRG/INTRAMURAL UNIT..ZRG7 MICROBIOMED CORPORATION AWARD AMOUNT......... $99,997 25315 461ST AVE HARTFORD, SD 57033 PERFORMING ORGANIZATION: MICROBIOMED CORPORATION TITLE ENDOGENOUS STENT FOR POSTANGIOPLASTY VASCULAR REPAIR ABSTRACT: Percutaneous transluminal coronary angioplasty (PTCA) and intravascular stenting are among the primary methods of choice to treat coronary artery disease (CAD). Limitations of long-term success include abrupt closure and restenosis, or chronic reclosure, of the vessel - both of which are associated with excessive vascular injury. Intravascular stenting has demonstrated moderate success in addressing these issues. However, current stents tend to be highly thrombogenic and immunologically stimulating. In this Phase I project we propose the novel application of a photochemically activated 1.8-naphthalimide dye in vascular repair following PTCA administration. By utilizing arterial wall and plaque proteins we may be able to produce an "endogenous" stent. Introduction and activation of the dye during a final balloon dilatation would cross-link the proteins in the dilated state and repair intimal or medial dissections resulting from the PTCA administration. In doing so, we may provide short- term structural support during the critical post-angioplasty period, as well as a physical barrier limiting exposure of subendothelium to circulating blood and vasoactive factors associated with the restenosis process. Initial results with these dyes in other tissues have yielded outstanding histological results with minimal cellular proliferation or extracellular matrix deposition and no inflammatory response. Phase II research will involve in vivo animal testing of the proposed "endogenous" stent with human testing and commercialization occurring in Phase III.