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.
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