Discovery of antimalarial drugs using humanized pseudo-liver immunodeficient mouse model

The two most important types are Plasmodium falciparum and Plasmodium vivax as they cause the greatest illness and death worldwide. One of the oldest drugs available to treat malaria is a drug called primaquine. Primaquine is a member of a class of drugs called 8-aminoquinolines. Primaquine treats the liver stage of malaria infection and will cure relapsing malaria. In fact, 8-aminoquinolines are the only class of molecules that cure relapsing malaria. However, there are some challenges with the widespread use of 8-aminoquinolines such as primaquine. The first is that drug causes hemolytic anemia, which is characterized by a temporary loss of circulating red blood cells. This occurs only in people with a genetically inherited mutation call Glucose Phosphate 6 dehydrogenase (G6PD) deficiency. The second challenge is that some people are not able to metabolize primaquine into its active form and because of that primaquine doesn’t work. Despite these limitations, the 8 aminoquinolines remain an important class of antimalaria drugs if a compound can be developed that overcomes these limitations. We have been working on antimalaria drug development and focusing on 8-aminoquinolines that can circumvent these challenges. A key piece of drug development is having preclinical models that mimic human diseases. As part of that work, we have developed an animal model to test for hemolytic toxicity. In this model, human red blood cells from people with the G6PD deficiency are transfused into a mouse that has no functional immune system. Because the mice don’t have an immune system, they cannot reject the red blood cells. When these mice are given primaquine, we can measure the loss of circulating human red blood cells. Thus, we have accomplished the validation and development of an important model that uses human cells.

Drug-based Strategies
Product Development

Aug 2016 — Sep 2020

$1.2M

United States