Single-Shot Malaria Treatment On The Horizon
Early research on a new malaria drug indicates it could be effective for treating and preventing the devastating disease, says an international team of researchers.
The drug, which is now undergoing Phase II clinical trials in humans, inhibits an enzyme essential to the survival of malaria.
If successful, the drug could be used as part of a single dose treatment regime, they report in the journal Science Translational Medicine .
“Treatments often fail because patients don’t take the full course of medication and that also contributes to the development of resistance,” says pharmaceutical scientist and senior author Professor Susan Charman of Monash University.
“This molecule has the potential to be effective after only a single dose which would be amazingly important for regions of poverty where compliance is a huge issue.”
Another desirable feature of the new drug is it kills both blood stages of the parasite as well as liver stages, says Charman.
“That is important because it could have use not only for treatment for malaria, but for preventing someone from getting sick in the first place,” she says.
Malaria infects 200 million and kills nearly 600,000, people across the globe each year, particularly children.
The disease poses a challenge for medical science because there is no proven vaccine, and the Plasmodium falciparum parasite that causes it, has developed resistance to most drugs used to treat malaria.
Even the front-line artemisinin-based therapies are showing signs of resistance, says Charman.
Professor Margaret Phillips of the University of Texas Southwestern Medical Center and colleagues previously identified a new class of drugs that inhibit a key enzyme in the malaria parasite called dihydroorotate dehydrogenase (DHODH).
“That’s why we really need a continual pipeline of drugs that hit new targets.”
“It’s an enzyme that’s essential for survival of the parasite because it’s involved in enabling the parasite to synthesise the building blocks of DNA and RNA,” says Charman. “So if that enzyme is inhibited by a drug the parasite can’t survive.”
Now, Charman, Phillips, and the team, including another Australian researcher Professor Vicky Avery of Griffith University, have identified that one molecule in the class, called DSM265, has potential as a powerful antimalarial.
They have carried out a series of tests on human and animal cells, as well as whole animals to test how safe and effective DSM265 is likely to be in humans.
The researchers have found that DSM265 kills malaria parasites in both blood and liver stages.
Once mosquitoes bites, parasites replicate in the liver cells before bursting out into the bloodstream.
“Having activity against those life stages is a big advantage,” says Charman.
“If you have given the drug to a healthy individual and an infected mosquito bites, the drug prevents the growth of the parasite in the liver so it doesn’t establish the infection.”
Another unique feature of the drug is that it is long-lasting and the researchers expect it could be active in humans for more than eight days.
“DSM265 is very slow to be eliminated from the body so effective concentrations are maintained for a very long period of time,” says Charman.
This shows the drug could have an edge on current anti-malarial treatments that require daily doses.
Repeated doses of the drug given to animals also showed no major side effects, report the researchers.
Last month, MMV, in collaboration with the Global Health Innovative Technology (GHIT) Fund and the Japanese pharmaceutical company Takeda, announced the start of Phase II trials on DSM265 in Peru.
DSM265 is the first DHODH inhibiter to reach clinical development for malaria treatment and could be given as a pill to adults and as a liquid to babies, says Charman.
To delay resistance to it, however, it would need to be administered in combination with another new drug that uses a different — as yet unknown — a mode of action.
“It’s a very exciting molecule,” she says. “We anxiously await the results of the clinical studies to find out if it is as effective and safe as we think it will be.”
“It’s got a long way to go but so far the results are very encouraging.”
The research was supported by the US NIH and the not-for-profit public-private partnership, Medicines for Malaria Venture in Geneva.
Some of the researchers, including Phillips and Charman, have patents on DSM265 but, says Charman, they have no commercial rights to any products.
“Since malaria is largely a disease that affects regions of poverty, there is usually no commercial focus to this research,” says Charman.
(Source: ABC Science (http://www.abc.net.au/science/articles/2015/07/16/4274162.htm)