IN RESPONSE TO THE REQUEST OF THE NATIONAL INSTITUTE OF ARTHRITIS, DIABETES AND DIGESTIVE AND KIDNEY DISEASES FOR RESEARCH INTO THE DIAGNOSIS AND TREATMENT OF "ORPHAN" INHERITED DISEASES AS OUTLINED IN THE OMNIBUS SOLICITATION FOR THE SMALL BUSINESS

IN RESPONSE TO THE REQUEST OF THE NATIONAL INSTITUTE OF ARTHRITIS, DIABETES AND DIGESTIVE AND KIDNEY DISEASES FOR RESEARCH INTO THE DIAGNOSIS AND TREATMENT OF "ORPHAN" INHERITED DISEASES AS OUTLINED IN THE OMNIBUS SOLICITATION FOR THE SMALL BUSINESS INNOVATIVE RESEARCH (SBIR) PROGRAM: IT IS THE AIM OF THE PROPOSED RESEARCH TO DEVELOP A LARGE SCALE PURIFICATION FOR HUMAN SPHINGOMYELINASE. CURRENTLY AVAILABLE PROCEDURES ARE INCAPABLE OF PRODUCING SUFFICIENT ENZYME FOR ANTIBODY PRODUCTION. THE DEVELOPMENT OF A COMMERCIAL DIAGNOSTIC KIT FOR THE "IN UTERO" IDENTIFICATION OF VARIANTS OF NIEMANN-PICK DISEASE BY AN ANALOGOUS METHOD TO THAT USED BY GINNS, ET AL (PROC. NAT. ACAD. SCI. USA 79, 5607-5610) FOR VARIANTS OF GAUCHER'S DISEASE, DEPENDS ON THEAVAILABILITY OF LARGE AMOUNTS OF HOMOGENEOUS SPHINGOMYELINASE. BASED ON EXPERIENCES DERIVED FROM THE LARGE-SCALE PURIFICATION OF TWO RELATED ENZYMES, GLUCOCEREBROSIDASE AND CERAMIDETRIHEXOSIDASE, A TWO STAGE PURIFICATION IS PROPOSED. IN THE FIRST PHASE EXTRACTION, VOLUME REDUCTION AND MODERATE PURIFICATION WILL BE REALIZED USING PRECIPITATIONS, ORGANIC EXTRACTIONS AND BATCH CHROMATOGRAPHY. A FINE PURIFICATION WILL FOLLOW IN WHICH COLUMN CHROMATOGRAPHY WILL BE UTILIZED TO YIELD HOMOGENEOUS ENZYME. IT IS EXPECTED THAT THIS PROCEDURE CAN BE WORKED OUT IN PRINCIPLE WITHIN THE INITIAL GRANT PERIOD.