Pushing the boundaries of biology

Three discovery teams led by Prof. Dennis Kyle, Prof. Elizabeth Winzeler and Dr Jetsumon Sattabongkot Prachumsri, and coordinated by Dr Brice Campo, MMV’s Director, Drug Discovery and Mélanie Rouillier, Senior Project Coordinator, will jointly receive the MMV Project of the Year 2016 award for their impressive progress in developing new assay platforms to test compounds for activity against the liver stages of malaria. These new assays are now making it possible to screen and identify novel compounds that could destroy the dormant stages and so prevent relapses. Relapses are especially dangerous, since they occur in the absence of a mosquito bite.

Brice and Melanie explain why this work is award winning, the challenges they encounter and where it will go from here.

Dr Brice Campo, MMV’s Director, Drug Discovery

1. Why is it important for MMV to be working on P. vivax malaria drug discovery?

There are many reasons: the relapse of P. vivax malaria represents a key area of unmet medical need. Currently there is only one medicine available to rid the liver of the dormant, relapsing form of the parasite (the hypnozoite). This medicine has been used for decades, and requires patients to take it for 14 days, even though they don’t feel sick anymore, so compliance is difficult. In addition, there is a risk of haemolysis in a small subgroup of patients, and this is something we’d want to address in the next generation of treatments.  

2. Why do you believe this research is award winning?

For more than 20 years the malaria research community has been waiting for an easy assay to enable the hunt for anti-relapse molecules. There was a blank page that needed to be filled. Today, new assays and tools have become available through our partners, making it possible to screen many thousands of molecules directly on hypnozoites, using parasites and host cells which are close to what happens in real disease. This is a real turning point for vivax research drug discovery.

3. How close are we to identifying the next anti-relapse molecule that could be optimized for further research?

The first screening campaigns, conducted together with our partners, have already identified potential hypnozoite-killer compounds, which are currently undergoing further validation. If their activity is confirmed, we could start optimizing these new molecules right away.

4. What are the next steps?

We are now capitalizing on the new assays. The goal is to move to a higher scale throughput in order to screen larger chemical libraries quickly. We are planning to screen up to 15,000 to 20,000 compounds directly on hypnozoites this year. We will also work with the winning research teams to set-up the new and exciting assays in other laboratories close to P. vivax patients; this will help streamline the process and increase our screening capacity. It will still be 2 or 3 years before we have a candidate to start preclinical development, though.

5. How did you feel when you found out your project was selected for the award?

I was very proud and happy for the teams. They have been working extremely hard, overcoming numerous challenges to get to where they are today. I am also personally honoured to receive this award. Having the assays up and running is the result of 6 years of hard work that has now come to fruition and this is only the beginning. The ultimate goal we continue to work towards is to deliver new anti-relapse medicines to the patients in need as fast as possible.

Mélanie Rouillier, Senior Project Coordinator

1. What is exciting for you about this project?

The project involves state-of-the-art science, pushing the boundaries of biology to go where no one has gone before. As a biologist, I find that really exciting.

2. Why do you think this project deserves the award?

The Plasmodium liver stage project is one of the MMV discovery team’s top priorities. It is extremely challenging, as the liver stage of the parasite is delicate and full of unknowns. Elizabeth, Dennis and Jetsumon are all pioneers in this area. They have each developed their own unique liver stage assay, each contributing to the potential discovery of new drugs active on the liver stage. Together with their teams, they all deserve the award for their innovative work and commitment!

3. As project coordinator, what was the biggest challenge you faced? How did you overcome it?

People got very excited about the first P. vivax liver stage assays, and many wanted to have their compounds tested. However, the logistics of the assays remain a major challenge: culturing P. vivax in the lab is not possible (not yet!), so these assays rely on actual patients infected with these parasites. Of course, this limits the capacity of the assays and results in long turnaround times to test compounds. People are looking forward to getting their data, but it will take some time. For me, that is one of the biggest challenges and it can only be overcome by managing people’s expectations.

4. How did you feel when you found out the project was selected for the award?

I was so happy for the three teams, and also so proud to be part of this project.