SBIR-STTR Award

Cryptosporidium parvum is a significant cause of diarrheal disease of human and veterinary importance worldwide. There is currently no effective, specific therapy approved for cryptosporidiosis. The overall goal of this project is to develop safe and effective, carbohydrate-based therapy for this disease. Carbohydrate-based therapy for a number of infectious diseases is being actively pursued in many laboratories and in clinical trials. The rationale for this type of therapy for cryptosporidiosis is based on the finding that C. parvum sporozoites express a surface lectin (carbohydrate binding protein) which binds to Galactose and N-acetylgalactosamine residues on host glycoconjugates such as mucins. Lectin-specific, intestinal as well as commercially available mucins and oligosaccharides-derived from them block attachment and subsequent infection of C. parvum in vitro. This raises the possibility that mucin oligosaccharides may be effective in abrogating infection in vivo. The specific aims of Phase I are directed at isolating and separating oligosaccharides from commercially available mucins. These oligosaccharides will then be evaluated for inhibition of cryptosporidial infection in vitro, using assays developed and standardized in our laboratory. Once oligosaccharides with high inhibitory capacity have been identified, they will be evaluated for therapeutic efficacy (in Phase 2) in vivo, in animal models of cryptosporidiosis. PROPOSED COMMERCIAL APPLICATIONS: Cryptosporidium is a water-borne disease of considerable human and animal (dairy and cattle industry) importance. There is currently no effective specific therapy approved for this disease. Carbohydrate- based therapy (which could potentially also be administered as a food additive) would be of potential commercial significance

Cryptosporidium parvum is a significant cause of diarrheal disease of human and veterinary importance worldwide. There is currently no effective, specific therapy approved for cryptosporidiosis. The overall goal of this project is to develop safe and effective, carbohydrate-based and lectin-based therapy for this disease. The rationale for this type of therapy for cryptosporidiosis is based on the finding that C. parvum sporozoites express a surface lectin which binds to Galactose and N-acetylgalactosamine (Gal/GaINAc) residues on host glycoconjugates such as mucins. Lectin-specific mucins and oligosaccharides-derived from them block infection of C. parvum in vitro. In addition, sporozoites express GaINAc-containing mucin-like surface glycoproteins which, are also involved in infection, raising the possibility that they too may serve as interventional targets. This is borne out by the finding that exogenous Gal/GaINAc-specific lectins, which bind to host and parasite mucins, have anti-cryptosporidial activity in vitro. The specific aims of Phase II are 1) To characterize and evaluate anti-cryptosporidial activity of mucin oligosaccharides in vivo in animal models of cryptosporidiosis; 2) To evaluate the therapeutic potential of exogenous levtins with specificity for parasite and host and mucin oligosaccharides in vivo 3) To identify and evaluate carbohydrate-based compounds from a combinedatorial library for anti-cryptosporidial activity in vitro