Description:
Reference #: 01236
The University of South Carolina is offering licensing opportunities for using ribose 5-phosphate isomerase inhibitors to treat against kinetoplastid parasites.
Background
Trypanosoma cruzi protozoa are the causative agent for Chagas’ disease, a neglected tropical disease that affects 6 – 7 million people worldwide. There are two treatment options available for Chagas’ disease and they include benznidazole and nifurtimox. These drugs have the potential for resistance because they were developed over 35 years ago and alternative drugs have not emerged. Trypanosoma brucei, which is the pathogen that causes Human African Sleeping Sickness and various drugs are available for the therapeutic treatment, such as pentamidine, suramin, eflornithine, and melarsoprol. Leishmania parasites are protozoa that cause the harsh skin disease leishmaniasis, and medical intervention requires treatment such as pentavalent antimony based medicines, or more expensive treatments such as amphotericin B, miltefosine, and paramomycin. The drugs for these kinetoplasid diseases all require substantial improvements in their tolerability, safety, and efficacy. A need exists for new drugs that can strongly interact with drug targets found in these parasites. Such a need includes inhibitors of the enzyme ribose 5-phosphate isomerase (RPI).
Invention Description:
Kinetoplastid parasites including T. cruzi, T. brucei and Leishmania spp., utilize and depend on the pentose phosphate pathway (PPP) for the reducing agent NADPH and also rely on the PPP for support of nucleic acid and nucleotide biosynthesis. The PPP is essential for these organisms and obstruction of the pathway leads to cell death and can be caused by inhibition (using a drug) of the enzyme, ribose 5-phosphate isomerase. In order to create a therapeutic drug, an inhibitor would need to selectively block the parasite homologue and avoid cross-reactivity with the human homologue (bind weaker or not bind at all), giving rise to a good selectively ratio. The subject invention is a set of drug compounds, which serve as strong selective inhibitors of T. cruzi ribose 5-phosphate isomerase (type B), as compared to the human homologue.
Potential Applications:
The drug compounds covered in this invention are to provide alternatives to current clinically used drugs.
Advantages and Benefits:
The drug compounds proposed in this patent may serve as viable substitutes for the currently used drugs in the clinic, pending in vitro parasite studies and mouse infectivity studies.