Page 62 - University of Pretoria RESEARCH REVIEW 2016

HEALTH
FINDING THE PATH
OF LEAST RESISTANCE
Drug resistance presents one of the biggest challenges in malaria control, and finding the path of least resistance is proving to be a challenging task.
Dr Bianca Verlinden’s specific focus is on slowing down drug resistance in the highly adaptive
malaria parasite, Plasmodium falciparum. She
is a postdoctoral fellow in the Department of Biochemistry, and works under the mentorship of Professor Lyn-Marie Birkholtz as part of the UP ISMC.
Verlinden and Birkholtz write that the malaria parasite is ‘an amazing shape shifter’ that over centuries has adapted to the habits of its victim (Conversation, November 2015) . Antimalarial
drugs have a limited lifespan because by changing
its DNA, the malaria parasite develops resistance with repeated exposure to antimalarial drugs. To tackle this problem, researchers are investigating potential antimalarial drugs with multiple targets to overwhelm the parasite and reduce the development of resistance.
In Verlinden’s research, the first step has been
to search for evidence in fields where resisting resistance may be possible: for example, in the fields of cancer and infectious disease, there are several innovative strategies used to delay resistance, especially in the multi-targeting approach that can take on several forms, such as combination therapies, hybrid drugs or integrated pharmacophores (multi- targeting drugs). Integrated pharmacophores
seem most promising in the development of new antimalarial drugs that have an enhanced ‘druglike’
EXCELLENCE REWARDED
Dr Verlinden’s research contribution resulted in her being chosen as one of the Top 100 Future Leaders of South Africa, from a pool of over 3 500 applicants, as part of the 2016 GradStar Awards Programme. In 2016 she was also chosen by the National Research Foundation as one of two excellent, young researchers
to represent the country at the 8th HOPE meeting with Nobel Laureates for the promotion of science, held in Japan. At this meeting she was chosen as the sole recipient of the prestigious HOPE Award for research excellence from among 109 young international scientists.
profile, but are multi-targeting. The analogy used
is that of a pharmaceutical skeleton key. Since an integrated ‘skeleton key’ is aimed at several different targets, it would exponentially be more efficient in resisting resistance, and more difficult for the cell
or microbe to adapt simultaneously to all targets, in comparison to a single drug target.
The antimicrobial skeleton keys that Verlinden studies are organic compounds known as polyamine analogues, which have been shown to inhibit the growth and regulation of target cells. She has previously screened three polyamine analogue libraries against sensitive and resistant strains of the pathogenic and transmissible stages of the malaria parasite. The majority of the polyamine analogues were highly active against both forms of the parasite. They also demonstrated excellent selectivity towards the parasite when compared to mammalian cells. The lead candidate demonstrated a multi-target mode of action that did not lead to parasite-resistant mutants, which provides proof of principle that the chemical structure of the lead polyamine analogue has the potential to limit resistance development in the malaria parasite.
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