A biting Anopheles mosquito: Malaria research is very complex
© Mauritius Images
According to WHO estimates, malaria killed around 627,000 people in 2012, the majority of which were children. That makes the mosquito-borne disease one of the most dangerous on earth. EMD Serono and the Medicines for Malaria Venture (MMV) have now joined forces in a pioneering project in the fight against malaria.
"Malaria", which comes from the Italian for "bad air", has had the tropical and sub-tropical regions of the world in its grip for thousands of years and has clearly influenced human development there. The World Health Organization (WHO) estimates that over 200 million people contract this febrile disease every year, which is primarily transmitted by mosquitoes of the genus Anopheles. It is usually associated with high, recurrent or periodic fever, shaking chills, gastrointestinal discomfort, and cramps. It can also quickly lead to coma and death, especially in children. There is still no effective vaccine.
Human beings serve as intermediate hosts to the pathogen, a parasite of the genus Plasmodium. The final host is the mosquito. After the infected mosquito bites, the pathogen moves to the liver of its human host. In this first stage, it matures and multiplies there before spreading throughout the bloodstream and ultimately attaching to the receptor molecules of red blood cells. After further growth, it triggers the periodic fever typical of malaria from within the blood of the human host. The cycle of this fever is 48 to 72 hours in duration, depending on which type of pathogen is involved.
Some of the pathogens develop further into their primary sexual form, the gametocytes. If a mosquito then bites the infected person again, it takes up these gametocytes, which mature into new pathogens inside the mosquito and are soon ready to spread new infection through its saliva. A minimum temperature of 15 degrees Celsius is required for the cycle inside the mosquito, which is why malaria primarily occurs in tropical areas of South America and Asia as well as Africa.
“Malaria kills a child every minute in Africa. New medicines are urgently needed.“
Over the last 100 years, the most effective way to fight malaria has proven to be "vector control", i.e., fighting the pathogens on a large scale with insecticides, as well as personal protection against mosquitoes. At the therapeutic level, combination drugs with artemisinin, which is obtained from the Chinese plant Artemisia annua, are the most effective treatment. The biggest problem here, however, is the emergence of resistance to artemisinin and related active ingredients. Reports of such resistance are now becoming increasingly common for Southeast Asia, which is putting the World Health Organization (WHO) on alert.
It is therefore all the more important to pursue new research and create new compound portfolios, such as the one being developed by the non-profit organization Medicines for Malaria Venture (MMV) with the support of EMD Serono. MMV sees its primary objective as discovering, developing, and making available new treatments for malaria, and also new medicines to protect vulnerable populations, particularly small children and expectant mothers. The ultimate aim is to support the eradication of the disease. "The malaria parasite is extremely agile and reacts very quickly to new active ingredients," says Beatrice Greco, who is Head of Malaria & Diagnostics in the recently created Research & Development department dedicated to Tropical diseases at EMD Serono.
"A range of different drugs that act in different ways are needed to fight Malaria. Furthermore, combination therapies are highly recommended by the WHO. So collaborations between organizations is essential to create the necessary variety of drugs." The main component of the cooperation between EMD Serono and MMV is, initially, a chemical series that caught the attention of researchers at EMD Serono during the screening of its library. "These synthetic molecules harbors enormous potential as a malaria drug, because they are especially suitable for use as a long-term active ingredient," says Beatrice Greco. "At an early stage in the research, we approached MMV with it and asked them whether they would be interested in a partnership, and whether we should join together to make this project a success."
Timothy Wells, Chief Scientific Officer at MMV, is enthusiastic and optimistic. "It is rare for a company to approach us with a molecule at this stage of research," he says. According to Wells, researchers had been looking for a while for a molecule which has the potential to remain active in patients for more than a week. A new medicine would need at least two such molecules, since each one protects the other against the emergence of resistance. "Now the job is to find out exactly what potential this molecule has for use in people," he says.
Normally this process would take at least four years. However, the MMV and EMD Serono team estimate that this could be done in just three years. New exciting experimental medicine models developed in Australia enable testing in volunteers with an extremely low level, sub-clinical infection. As well as being faster, it’s a way of rapidly testing on people who are completely naïve from an immune perspective: knowing that the final patients, African children, also have no immune protection. Although the research on the molecule is still at an early stage, the partners EMD Serono and MMV are both enthusiastic. "We are still in an early stage, but the program was launched with great energy and has been eagerly welcomed — including by the scientific advisory committee of MMV, to which we have presented the project twice now," says Beatrice Greco.
The cooperation with MMV is one of a series of projects that marks the successful launch of a new form of organization, the external Translational Innovation Platform (eTIP) Global Health. Interdisciplinary approaches involving different divisions of the company — such as EMD Millipore with its developments in diagnostics, or the research groups involved in the insect repellent IR3535 — are opening new doors in the fight against tropical diseases such as malaria or schistosomiasis. "We have experts that we can rely on in every field that is needed," says Jutta Reinhard-Rupp, Head of eTIP Global Health. "When it comes to fighting resistances, you have to cover all the bases. You need insect repellents as well as diagnostics and combined drug therapies. Offering the right treatment for the right patient and against the right pathogen - that is one of the big jobs we have taken on."
Michel Revel dedicated his life to the search for MS treatments. He also founded Israel’s biotech industry.