Deaths from malaria

Dr Gary Evans

Malaria is a mosquito-borne infectious disease that results when a person’s red blood cells are overrun by parasites of the Plasmodium genus after they’ve been bitten. Depending on which report you read, somewhere between 655 000 (World Health Organization, 2011) and 1 238 000 people (Lancet, 4 February 2012) are estimated to have died from malaria in 2010 – an alarming figure either way.

Vaccine resistance

At present, there is no long-term vaccine for malaria, and although different treatments are available, the parasite often becomes resistant or immune to them. Efforts to fight malaria have historically focused on preventative measures such as draining stagnant water where mosquitoes can breed and providing people with mosquito netting.

Anti-malarial compound BCX4945

IRL’s Carbohydrate Chemistry Group led by Dr Gary Evans is part of an international team that has managed to synthesise an anti-malarial compound, currently known as BCX4945, which has successfully passed the first stage of a preclinical efficacy study.

The compound targets a particular species of parasite known as Plasmodium falciparum.

“About 90% of all [malaria-related] deaths worldwide are caused by the protozoan parasite Plasmodium falciparum,” says Dr Evans.

“Early efficacy trials have shown that BCX4945 clears the parasite responsible for malaria within 7 days,” he says.

People infected by P. falciparum will often suffer from severe shivering every 36–48 hours. Coma and death can result if the parasite goes untreated, with brain damage due to anaemia common among children.

How the compound works

“The parasite is relatively unusual in that it’s a purine auxotroph, meaning that it sources organic compounds known as purines from its host,” says Dr Evans.

The new drug blocks the enzyme used by the parasite to harvest these compounds and so the parasite can no longer multiply and overwhelm the host’s immune system.

“It’s a numbers game – they build millions of themselves,” Dr Evans says. “If you keep that number small, then the host immune system can simply manage the infection.”

Years of clinical trials ahead

The positive trial results give hope that BCX4945 may become a valuable addition to the existing arsenal currently used in the treatment of the disease, although its development as a drug available to patients is still many years away.

“The other drug candidates we are involved with have spent as many as 10 years in preclinical and clinical trials,” says Dr Evans.

IRL has licensed BCX4945 to BioCryst Pharmaceuticals Inc in the USA. In addition, the drug’s progress is being followed closely by New Zealand’s burgeoning pharmaceutical industry, including New Zealand Pharmaceuticals Ltd (NZP), which possesses the capability to manufacture the drug’s active pharmaceutical ingredient.

Scientific and industrial collaboration

“We look forward to watching the clinical progress of BCX4945 and hope to manufacture it as our contribution to the future of this malaria drug,” says NZP Ltd Business Development Manager Selwyn Yorke.

The project is led by Professor Vern Schramm from the Albert Einstein College of Medicine, although the initial discovery of BCX4945 was achieved by IRL’s Carbohydrate Chemistry Group. Dr Evans says the further development of the drug to this point “has been an excellent example of scientific and industrial collaboration”.