New malaria drug unleashes an immune system assault on infected cells

Howard Hughes Medical Institute investigator Joseph DeRisi is working on a new malaria treatment that makes infected red blood cells an inviting target for the human immune system. And the team behind the effort is ramping up a human safety study in healthy volunteers as the first step in the clinical journey to prove its effectiveness.

Working with mouse models for malaria, DeRisi and colleagues at St. Jude Children's Research Hospital found that by inhibiting the ATP4 protein the infected red blood cells need to survive, the cells would shrink and grow rigid, hallmarks of aging that trigger their elimination by the immune system.

The investigators were working with a drug dubbed (+)-SJ733, which was found after they sequenced the genome of the most lethal of the parasites that spreads the disease through mosquito bites. The drug is part of a wider class of therapies called spiroindolones, which also targets the ATP4 protein. The drug class includes NITD246, which is already being studied in the clinic. (I wrote about some of the work in the field 4 years ago.)

A consortium involving St. Jude, Medicines for Malaria Venture and Japan's Eisai are supporting the clinical work ahead.

Like many diseases that afflict poor countries, malaria hasn't earned the kind of big budgets devoted to cancer and diabetes therapies. GlaxoSmithKline ($GSK) has been advancing a new vaccine, but it offers only modest protection, leaving a threat in place that kills one person every minute in Africa. Nonprofit groups, though, have been helping to change things, and a number of investigators have committed considerable time and attention to the challenge.

"Our goal is to develop an affordable, fast-acting combination therapy that cures malaria with a single dose," said corresponding author R. Kiplin Guy, chair of the St. Jude Department of Chemical Biology and Therapeutics. "These results indicate that SJ733 and other compounds that act in a similar fashion are highly attractive additions to the global malaria eradication campaign, which would mean so much for the world's children, who are central to the mission of St. Jude."

- here's the release