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Compounds and methods for treating mammalian gastrointestinal parasitic infections


Fighting Protozoan Infections

The Situation: Cryptosporidium parvum is a waterborne protozoan which infects the intestinal tracts of human, causing persistent diarrhea and enteritis. Chronic Cryptosporidium infection results in a severe and life-threatening condition in patients with AIDS.

Our Solution: We have identified 10 potent and highly selective small-molecule inhibitors of Cryptosporidium parvum that effectively slow or block the proliferation of this parasite in human and mammals.

Background

The protozoa Cryptosporidium parvum is an important human pathogen causing severe gastrointestinal disease. Small children, pregnant women, the elderly, and immuno-compromised AIDS patients are at risk of chronic and often fatal infection. C. parvum produces oocysts that are highly resistant to water chlorination. People ingest these oocysts, which then “hatch” in their bodies. Several large outbreaks in the U.S. have been linked to drinking and recreational water. Infection rates are extremely high, with disease manifest in 30% of exposed individuals and a 50-70% mortality rate among immuno-compromised individuals. Effective drugs are urgently needed for treating C. parvum infections in AIDS patients and for managing epidemic outbreaks.

Applications

  • Treatment for parasitic protozoan infection in AIDS patients.

Advantages

  • 10 potent inosine-5’-monophosphate dehydrogenase (IMPDH) inhibitors have been identified to inhibit C. parvum IMPDH.
  • These compounds selectively inhibit parasite IMPDH over human IMPDH, providing effective and safe treatment for patients.

Technology

The invention provides pharmaceutical compositions and methods that slow or block protozoan parasite proliferation in human and mammals by selectively inhibiting protozoan inosine-5’-monophosphate dehydrogenase (IMPDH). All parasitic protozoa lack purine biosynthetic enzymes and must salvage purine from their host, making this pathway an extremely attractive target for developing anti-protozoal drugs. IMPDH is a key enzyme in the purine salvage pathway. The investigators have shown that: (1) IMPDH inhibitors block parasitic proliferation in vivo; and (2) the protozoa C. parvum IMPDH has very different properties than that of the human enzyme, allowing the screening for inhibitors specifically against protozoan IMPDH. A commercial library containing 44,000 compounds were screened at the National Screening Laboratory for the Regional Centers of Excellence in Biodefense and Emerging Infectious Disease (NSRB), and 10 compounds were identified to be potent specific inhibitors of C. parvum IMPDH. The invention provides possible novel and effective treatments for the many devastating diseases caused by protozoan infections.

Patent Status

  • Patent pending in United States
  • Pending international patent application

Inventors

Lizbeth Hedstrom and Boris Striepen.

To discuss this technology with a licensing officer, please call Irene Abrams at (781)-736-2176 or email iabrams@brandeis.edu and ask about record ID: 2006-0303.