A new single-dose malaria drug is offering promise as both a cure to malaria and also a way to prevent the disease according to researchers at UT Southwestern Medical Center. The new drug, which is known as DSM265, kills the drug-resistant malaria parasites in the blood and liver by targeting the ability of the parasites to replicate.
Malaria is a very infectious disease that is transmitted by mosquitoes, and it kills about 600,000 people worldwide every year. Most of the people who are killed by malaria are under 5-years-old, and it’s more common in sub-Saharan Africa. Almost 200 million cases of malaria are reported every year, with about 3 billion people in 97 countries at risk for the disease. Lead author Dr. Margaret Phillips, who is a professor of Pharmacology at UT Southwestern said that this could be the first single-dose cure for malaria, and would be used in partnership with another drug. This drug could also be developed into a once-a-week preventive vaccination as well, and the results of the study were just published in Science Translational Medicine. Not only was UT Southwestern involved in the research study, but Monash Institute of Pharmaceutical Sciences in Australia, the University of Washington, and the not-for-profit Medicines for Malaria Venture was also involved.
The researchers were able to determine that the DSM265 compound killed the malaria parasite Plasmodium in both the blood stage and liver stage of infection. The compound was also shown to be well tolerated by the body and effective in the preclinical models. The current anti-malarial treatments are artemisnin-based combination therapies, also known as ACTs, and they are part of why malaria has declined in recent years. The malaria strains that are resistant to this therapy are now popping up in more places, including Thailand, Cambodia, Vietnam, Laos, and Myanmar. Dr. Phillips said that we are seeing more drug resistance and this is taking out every one of the anti-malarial drugs that are being used. Dr. Phillips holds the Beatrice and Miguel Elias Distinguished Chair in Biomedical Science, and also the Carolyn R. Bacon Professorship in Medical Sciences and Education. The parasite that is involved in malaria is adapting every day and becoming resistant to drugs, and this is inevitable at this point. The thing now is to make and deliver new modes of action and safeguard the longevity of the anti-malarial through using it as a combination for as long as possible.
In order to help combat the drug-resistance, the DSM265 drug would be mixed with another new drug and then used as a one-dose combination therapy. There could also be another option which would be to make DSM265 a once-a-week preventive treatment for people who are traveling to the malaria-endemic countries or for people who are living in places where the malaria infections are seasonal and the human immunity is low. While both of these scenarios sound good, it will be a long time away from now before either of the choices will be available, and it depends on the outcome of both the current trials and future trials. The good thing about DSM265 is that it targets the ability of the parasite to synthesize the nucleotide precursors, and these are required for synthesis of both DNA and RNA. The DSM265 was safely tolerated in the non-human tests, The study also concluded that there is an optimal dosing level and strength that makes the drug effective in the preclinical models, which helps estimate the dosing for humans, and that helps pave the way for the human clinical trials. The first clinical trial safety study was in Australia, and there has been an ongoing efficacy study in Peru, which helps evaluate the ability to treat patients with malaria.
There are more human studies being planned, including one that will test the drug as a preventive medicine. UT Southwestern will be assisting in an advisory capacity for the upcoming studies. For now, the researchers are hopeful that the future studies will also show the drug to be effective as both a preventive treatment option and a treatment to cure the disease. The best way to move forward is to keep this as a combination drug for as long as possible, but it’s not known just how long the combination therapy would work before the parasite becomes immune to that as well. The next step is to get more clinical trials going and get the approval for human clinical trials, but even if all of those trials go well and there are no bad side effects to the medication, it will likely be at least 5 years before this drug would be used commercially in humans. It is also not known how much this medication would cost or if there would be ways people could offset the cost of the therapy, and then you have to think about whether or not insurance companies would cover the cost, and if so, how much would be out of pocket. So while this all sounds promising, there are still a lot of questions that need to be answered before we see this medication being used regularly to help people who have malaria or who are at risk for developing the disease.