August 29, 2019

expert reaction to study looking at a potential new drug for malaria

A study, published in Science, reports the discovery of a new drug that me able to stop the spread of malaria and treat those suffering from the disease.

Prof Jake Baum, Professor of Cell Biology and Infectious Diseases, Imperial College London, said:

“We stand at a key cross-roads in malaria control and eradication. There is rising drug resistance in South East Asia and we have stalled in our efforts to reduce malaria incidence globally. As such, there is an urgent need, just like with antibiotic resistance, to find new drugs with new modes of action. This is where the current study fits in, looking at an exciting class of drugs that indeed works in a new way. So far, in this discovery paper, the authors show the drug has robust activity, targeting the malaria parasite at several stages in its lifecycle. It is still very early in development and there’s a long way to go before these drugs would even be put into testing in humans, but we need a full pipeline for the long road if we are to achieve global eradication. 

“This is not the first time a malaria drug has been found with the ability to target several stages in the parasites lifecycle, but where these drugs differ from the existing ones is the way they act, targeting a previously untested parasite protein PfCLK3. This is therefore a brand new class of antimalarial drug and a new avenue to explore. Part of the proof and discovery process for any new target is artificially evolving drug resistance in the malaria parasite itself. This does always raise a question in my mind, if you can evolve resistance in the lab, surely nature will do it too (think Jeff Goldblum in Jurassic Park). To my mind, this means resistance can be expected to evolve. As such, multi-stage activity, whilst exciting, isn’t necessarily the be-all and end-all of drug discovery, since if a resistant parasite emerges, it will likely be resistant at every stage. I think most people are well-aware of this, which means that any new drug will always be a part of a combination, where two drugs acting together on different targets makes it much less likely for resistance to evolve. So, this is a new drug that could prove to be a powerful partner for other antimalarials. For that to be realised, we will need to know a lot more about how long the drug lasts, how quickly it acts and how well it formulates so that it (or more likely a derivative) can be given to people that need it. This is the long road of drug development that must clearly now start with any drug such as this. So, we should celebrate having a new weapon in our armamentarium but see this as part of a large cohort of drugs that all need to be advanced so we never run out of options to treat a sick child.

“A case in point is Artemisinin. This ancient Chinese herb, now front line Nobel prize winning wonder drug for malaria is failing and with it, several of the combination drugs are too. That’s multi-drug resistant malaria and that’s scary. If a parasite resistant to several front line drugs arrived in Africa (where most deaths from malaria are) we’d be in trouble. So, we need not just a replacement but a pipeline of replacements. It’ll always be a revolving door – new drugs in, old ones out (as nature always finds a way to evolve resistance). Provided that these new anti-PfCLK3 drugs have good drug properties in vivo (in animals and then humans), show good safety and can be formulated with other partners then this is a major advance and we should celebrate another malaria drug journey starting. Such drugs are worth pursuing and we should hope they make it to the clinic. But we should be clear, no drug alone will eradicate malaria.”

Michael Chew, Infection and Immunobiology Portfolio Manager, Wellcome said:

“This research is a major step in developing potential new treatments for malaria. Currently there are only a few effective drugs left but they mainly target only specific stages in the parasite life cycle and face the growing threat of drug-resistance. This study has identified a compound that disrupts a specific target on multiple species of the malaria parasite, at each stage of the life cycle. This effectively kills it before it can cause disease, or be transmitted to others via mosquito bites.

“It needs to now be developed further and be tested in clinical trials. If successful this could lead to urgently needed new drugs to tackle malaria, which affects around 200 million people each year.”

‘Validation of the protein kinase PfCLK3 as a multi-stage cross species malarial drug target’ by Alam et al. was published in Science at 19:00 UK time on Thursday 29 August. 

Declared interests

Prof Jake Baum: None

Michael Chew: “Wellcome funds the Wellcome Centre for Integrative Parasitology”