New Compound Boosts Older Malaria Drugs, Prevents Drug Resistance, Study Says
A new malaria drug called T3.5 effectively kills malaria parasites and helps protect against the development of drug resistance, according to a study published online Wednesday in the journal Nature, Reuters reports. The study also found that T3.5 improves the efficacy of older malaria drugs during tests in mice (Fox, Reuters, 4/8). According to Don van Schalkwyk, a malaria researcher at the Australian National University, T3.5 is the first compound to combine the ability to kill malaria parasites with the capacity to boost the efficacy of older drugs against both drug-resistant and drug-sensitive parasites. Van Schalkwyk said these properties are "highly advantageous given that any malaria-endemic region is likely to contain a malaria parasite population with diverse drug sensitivity."
According to the Oregonian, malaria parasites enter red blood cells and feed on hemoglobin, which are protein red cells that carry oxygen. Older malaria treatments, such as quinine and chloroquine, work by preventing the parasites from neutralizing a toxic byproduct of hemoglobin. However, drug-resistant parasites persist by pumping these drugs out of their digestive sacs. To address this issue, Jane Kelly of the Portland Veterans Affairs Medical Center and colleagues developed T3.5, a compound that maintains the toxicity of the hemoglobin byproduct in the same way as quinine and chloroquine but also hinders the parasite's ability to pump drugs out of its digestive sac.
After testing the compound, the researchers found that T3.5 combined with quinine successfully eradicated malaria in mice when using one-third of the quinine dose required if the older drug were administered alone. Michael Riscoe, study co-author, said laboratory and animal tests indicate that T3.5 is "highly synergistic with quinine and newer drugs, even in parasites that are not yet resistant" (Rojas-Burke, Oregonian, 4/8). According to Kelly, the study demonstrates that T3.5 is "intrinsically potent" when used alone, "and in combination with other antimalarials it is synergistic" by helping to boost older drugs (Reuters, 4/8).
Leann Tilley -- a biochemistry professor at La Trobe University in Melbourne, Australia -- who was not involved in developing T3.5 -- called the study "a major development in our effort to treat this lethal human pathogen." In addition, the compound is relatively inexpensive to produce, and affordability is an important factor when developing malaria drugs, Tilley said. Although it "will be quite a long way yet" before scientists conduct human trials on T3.5, the researchers "have great confidence in these drugs," Kelly said. She added that "preliminary safety and toxicity results are very encouraging." According to Riscoe, if clinical trials demonstrate that T3.5 is safe and effective for humans, physicians could combine the new compound with older drugs that are safe and affordable. However, the research team will need to secure further funding to advance their studies on T3.5, the authors said (Oregonian, 4/8).
An abstract of the study is available online.