Antimalarial drug discovery - the path towards eradication.

Malaria is a disease that still affects a significant proportion of the global human population. Whilst advances have been made in lowering the numbers of cases and deaths, it is clear that a strategy based solely on disease control year on year, without reducing transmission and ultimately eradicating the parasite, is unsustainable. This article highlights the current mainstay treatments alongside a selection of emerging new clinical molecules from the portfolio of Medicines for Malaria Venture (MMV) and our partners. In each case, the key highlights from each research phase are described to demonstrate how these new potential medicines were discovered. Given the increased focus of the community on eradicating the disease, the strategy for next generation combination medicines that will provide such potential is explained.

The antimalarial pipeline.

Over the past decade, new high-throughput phenotypic assays with malaria parasites have been developed, and these were used to screen millions of compounds. This effort, as well as improving older chemical scaffolds and optimising compounds against both known and new drug targets has resulted in the discovery of exciting new pipeline drug candidates that are now being evaluated in a number of clinical trials. In addition, the pitfalls and opportunities from this experience has led to a better definition of the optimal target compound and product profiles for new antimalarials, including medicines that treat uncomplicated or severe malaria, provide chemoprevention, or stop disease transmission, covering all stages of the parasite. An important decision element is how to combine these new molecules with existing ones in today's dynamic resistance landscape.

New biological therapies from the human genome.

Over the past 20 years, the biotechnology industry has been extraordinarily successful in bringing a wide variety of new products to the market, including recombinant versions of natural proteins such as growth hormone, insulin and the gonadotropins. The availability of the human genome sequence has given us the chance to identify the entire catalogue of human secreted proteins, often called the secretome. One of the challenges of biotechnology research has been to identify the biological activities of these proteins and to identify if any of them could have a therapeutic or pharmacologic use. The paradigm has effectively been reversed, in that it used to be easy to know the biological activity, but difficult to clone, whereas now the contrary is true. Five years on, it is clear that finding new biological activities is a very difficult process. Much of the ground gained in this period has either been through the development of antibodies as therapies or by the use of protein engineering to produce better versions of the proteins that are already being produced.