SBIR-STTR Award

Toxoplasmosis is a serious disease in congenitally infected infants and in immunocompromised patients. Millions of dollars are needed each year to care for victims of congenital toxoplasmosis in the United States alone, and toxoplasmic encephalitis is now the most commonly recognized cause of opportunistic infection of the central nervous system in patients with AIDS. Toxoplastna gondii, a parasite with worldwide distribution, is also a pathogen of significant economic importance in sheep and swine where it causes abortion. Artemisinin (Qinghaosu) and certain derivatives have shown significant antiparasitic activity for the related diseases of malaria and toxoplasmosis. Expanded evaluation of other functional derivatives and correlation of results to pharmacological factors leading to high efficacy and low toxicity is a necessary step toward commercialization of an effective agent. The immediate research will focus on functional derivatives of Artemisinin at the C-12 position which will be chemically synthesized and evaluated for inhibition of growth of Toxoplasma gondii by published methods. We have a supply of Artemisinin on-hand for starting material, have successfully synthesized other derivatives, have published inhibition studies on T. gondii, and have the necessary technical background to interpret the results as precedence for further research and commercialization.Awardee's statement of the potential commercial applications of the research:This research is intended to lead to the development of one or more highly effective, yet safe drugs for the treatment of Toxoplasmosis, without the high incidence of toxicity associated with the current treatment regimen. Toxoplasma gondii is a parasite with a worldwide distribution, is responsible for more than 20,000 cases of toxoplasmic encephalitis in patients with AIDS in the Unites States alone, is a major problem in all patients which are immuno-compromised, severely affects children with congenital infections and causes abortion in sheep and swine.National Institute of Allergy and Infectious Diseases (NIAID)

Toxoplasmosis and cryptosporidiosis are the most common causes of hospitalization and opportunistic infection in patients with AIDS. Toxoplasma and Cryptosporidia, parasites with worldwide distribution, are also pathogens of significant economic importance in livestock where they cause abortion, diarrhea, weight loss and death. Artemisinin (qinghaosu) and certain derivatives have shown significant antiparasitic activity for the related disease malaria and for toxoplasmosis and cryptosporidiosis in Phase I SBIR and independent studies. Synthesis and evaluation of additional derivatives followed by correlation of results to pharmacological factors leading to high therapeutic index are necessary steps toward commercialization of an effective agent. The research will focus on C-12 and endoperoxide functional derivatives of artemisinin that will be synthesized and evaluated for inhibition of growth of Toxoplasma gondii and Cryptosporidium parvum by proven in vitro and in vivo methods. We have a supply of artemismin on hand, have successfully synthesized derivatives, have the necessary technical background to interpret results, have proven natural product and derivative GMP manufacturing capabilities, and are committed to participate in commercialization. The Phase II program meets the technical objectives of a recent NIAID call for the discovery of drugs for the treatment of opportunistic infections associated with AIDS.Awardee's statement of the potential commercial applications of the research: The research is designed to identify Toxoplasma and Cryptosporidia, parasites with worldwide distribution, and pathogens of significant economic importance in immunocompromised humans and livestock, where they cause abortion, diarrhea, weight loss and death. Toxoplasmosis and cryptosporidiosis are the most common causes of hospitalization and opportunistic infection in patients with AIDS. The current treatment regimen for toxoplasmosis is characterized by toxicity and eventual failure. No effective treatment exists for cryptosporidiosis.National Institute of Allergy and Infectious Diseases (NIAID)