Targeting Cysteine Proteases--Antiparasitic Chemotherapy

Sponsor: NIH National Institute of Allergy and Infectious Disease

Location(s): United States


Cysteine proteases have been identified as promising targets for the development of antiparasitic chemotherapy. An attractive aspect of these enzymes is their widespread importance in both protozoan and helminth parasites of domestic animals and humans. Concerns about the ability to selectively inhibit parasite proteases without affecting host homologues have been addressed in recent studies of Trypanosoma cruzi and Plasmodium falciparum. Significant data on half-life, metabolism, pharmacokinetics and safety have been accumulated. Differential uptake of proteases by parasitic organisms versus host cells, and relatively less redundancy in parasite protease gene families, may be two factors which contribute to the successful treatment of animal models of infection.

The Center for Discovery and Innovation in Parasitic Diseases (CDIPD) is an interdisciplinary research center based at UCSF. CDIPD targets diseases affecting hundreds of millions of people worldwide, but which are largely ignored by traditional drug and vaccine discovery companies because they primarily affect the poor and underserved.

CDIPD was inaugurated as the Tropical Disease Research Unit at UCSF in 1985. This TDRU was supported by the National Institutes of Allergy and Infectious Diseases, and focused on drug development, targeting a protease of Trypanosoma cruzi. The interdisciplinary science that now characterizes the Center grew from this initial effort. Members of the TDRU included chemists, computational scientists, structural biologists, biochemists, and parasitologists.

In 2002, Herb and Marion Sandler made a groundbreaking gift to the University of California to expand the TDRU into the Sandler Center for Basic Research in Parasitic Diseases. This now allowed the interdisciplinary research group to branch into several other parasitic diseases of global health importance. By 2009, the focus of this research team became the discovery and development of drugs for several neglected parasitic diseases. The Sandler Center became the Sandler Center for Drug Discovery.

The most recent transition in 2012 to the Center for Discovery and Innovation in Parasitic Diseases (CDIPD) reflects a broader interdisciplinary research effort that now includes not only drug discovery and development, but also vaccine development and collaborations to identify biomarkers of parasitic diseases.