With our sights firmly set on malaria elimination/ eradication, MMV’s strategy has evolved. Our discovery work is focused on the need for novel medicines able to treat relapsing (Plasmodium vivax) malaria and block transmission. Yet at the same time we must stay a step ahead of the parasite; history tells us it is incredibly adaptable, having become resistant to each medicine sent to assail it.
With these goals in mind MMV has worked with six pharma companies (GSK, Sanofi, Novartis, Pfizer, Genzyme and AstraZeneca) and numerous academic institutions (e.g. University of Cape Town (UCT), Dundee University and St Jude Children’s Research Hospital) to screen more than six million compounds. This has resulted in over 25,000 promising molecules to populate the pipeline.
Furthermore, in a bid to catalyse malaria and neglected disease drug discovery, MMV has launched a Malaria Box with 400 structurally diverse available compounds from this screening campaign. The MMV Malaria Box is being made to available researchers at no cost.
1. What has been achieved to date?
We have screened 40,000 small molecules from a commercial library (BioFocus). Compounds that killed the parasite and possessed the most promising properties were selected. The initial goal was to demonstrate pharmacological proof-of-concept by testing these select compounds in a laboratory model of malaria. We are now working on a series that has shown activity in a laboratory model of malaria. A single (low) oral dose of one of the front-runner compounds provided a complete cure in the model and shows potential as a clinical candidate.
This is an outstanding result because clinically used drugs such as chloroquine, the artemisinins and mefloquine require multiple doses to achieve the same cure.
2. What does South Africa bring to the table?
South Africa is arguably the most technologically and economically advanced country on the African continent. We have a wealth of talent in various scientific disciplines relevant to drug discovery and a strong reputation in basic science and clinical studies for infectious diseases. The country really has a lot to offer.
However, despite a number of drug discovery programmes being initiated in various institutions and organizations in South Africa in the last 5 years or so, the serious lack of a critical mass of individuals with pharmaceutical industry experience in key areas such as medicinal chemistry and drug metabolism disciplines, threatens to render current efforts unproductive. This issue is being addressed through our centre, H3-D, where we have embarked on recruiting experienced personnel from the pharmaceutical industry.
3. What is the advantage of working with MMV on a project of this kind?
MMV has a huge network of partners, which is partly what makes this project unique. We can integrate medicinal chemistry from UCT with preclinical pharmacology and drug metabolism from Monash University, Australia, and parasitology expertise from Swiss TPH. We can then screen a huge volume of compounds with engineering technology from Eskitis (Griffith University). This volume would just not have been possible a few years ago. Medicinal chemistry is about understanding what the liabilities are and how you can use chemistry to overcome them. This expert multicentre team really provides all the information that a medicinal chemist needs to determine which molecules to take forward and to move quickly.
The MMV project has also been critical to building infrastructure at UCT and we are now on our way towards being able to conduct integrated antimalarial drug discovery with parasitology, medicinal chemistry and drug metabolism all at UCT.
Prof. Kelly Chibale is the Founder and Director of the University of Cape Town’s Drug Discovery and Development Centre (H3-D), South Africa.