Feature: Restocking the medicine cabinet
26 April 2007. By Ian Jones
Whichever way one looks at the statistics on tropical diseases, the need for prevention and cure is all too apparent: malaria alone threatens 2 billion people, causes losses of more than £8bn in annual gross domestic product in Africa and kills a child every 30 seconds. With the genomes of many important pathogens now sequenced, our understanding of pathogen biology and host responses is growing all the time. Yet the conversion of these insights into practical therapeutic tools is frustratingly slow. This bottleneck is a major focus of the Wellcome Trust's Technology Transfer activities.
"There's a desperate need for new drugs," argues Ted Bianco, Director of Technology Transfer at the Wellcome Trust. "There's a lot of high-quality research being carried out but we need to make sure people actually benefit."
The drug deficit for neglected diseases is the result of many factors. On the one hand, the harsh reality is that there are few market incentives for the development of medicines to combat diseases typically affecting the poorest people in developing nations. Even when drugs are developed, they often prove to be too expensive.
On the other hand, there are increasing standards to be met in the research and development of new drugs before venture capitalists and pharmaceutical companies are willing to get involved. It is no longer sufficient for a researcher to come up with a promising possible drug target or novel chemistry. Such basic research is regarded as too high-risk to attract commercial interest. Scientists must now have solid evidence of a biological effect - enough to fulfill intellectual property requirements - and a refined compound (an optimised lead).
It is clear, then, that bridging the gap between basic research and commercial application in drug development will require innovative solutions. Drug discovery is a major focus of the Trust's Technology Transfer activities, seeking to maximise the impact of new research on healthcare with a diverse portfolio of projects that encompasses medical devices, diagnostics, enabling technologies, therapeutics and vaccines.
Neglected diseases
One potential solution, says Rick Davis, a Senior Business Analyst, is to bring the expertise normally found in industry into an academic setting, so more of the early stages of drug discovery can be carried out with no commercial risk. This is the case for an innovative initiative at the University of Dundee, which was recently awarded £8.1m funding through a Technology Transfer Strategic Award.
Professors Mike Ferguson and Alan Fairlamb at the Centre for Interdisciplinary Research at Dundee work on neglected diseases such as African sleeping sickness, leishmaniasis and Chagas' disease. The new initiative extends their reach from parasite biology to drug design, synthesis and testing. By recruiting staff with industry experience, Dr Davis points out, Dundee is taking the unusual step of setting up a drug discovery programme in a university environment.
In a complementary venture, in May 2006 the Trust also pledged - jointly with the Medicines for Malaria Venture and the Singapore Economic Development Board - over £10m towards the search for a single-dose cure for the most dangerous form of malaria, Plasmodium falciparum, and a new cure for the most common form of malaria, P. vivax.
The project is a joint venture with several research institutions, and is managed at the Novartis Institute for Tropical Diseases (NITD) in Singapore under the directorship of Professor Alex Matter. With an impressive track record in drug development - including kinase-based drugs for leukaemia (Glivec) and gastrointestinal cancer - Professor Matter moved to NITD in 2003 as its inaugural Director. "His leadership is likely to be crucial to the success of the programme," suggests Dr Davis. The programme will hand on promising candidate drugs to the Medicines for Malaria Venture for development to market.
The NITD joint venture is a good example of the key elements of the model of translational research promoted by the Trust, says Dr Davis. It focuses both on a specific health challenge - the fight against malaria - and on a realistically deliverable and affordable drug regimen - a single-dose cure. And it is carried out by a multidisciplinary research team with academic and industry experience.
This project also illustrates a growing trend: the importance of public-private partnerships (PPPs) in drug development. According to Dr Mary Moran at the London School of Economics, who led a Wellcome Trust-funded study, this mode of product development is cost-effective and relatively efficient for pursuing new tools to fight the most neglected diseases. 1,2
Building broader bridges
Even in the West, the delivery of new drugs has slowed over the past two or three decades, despite massive investment by the pharmaceutical industry. At the same time, the landscape of drug development has evolved, with the emergence of a thriving biotech industry and with academic centres putting greater emphasis on commercialisation of research.
The Wellcome Trust's main contribution to this emerging landscape is the £91m five-year Seeding Drug Discovery initiative, which aims to facilitate the development of small molecule therapeutics in areas of unmet medical need.
Typically, says Dr Davis, the principal investigator will have expertise in the biology or biochemistry of a disease, but they may not have the skills in the practical application of that knowledge. By fostering engagement between scientists from complementary academic disciplines - as well as between this community and the biotech sector, venture capitalists and the pharmaceutical industry - the initiative emphasises the productivity of interdisciplinary working.
The products of this interdisciplinary research will include promising preclinical drug candidates and a wide range of new research assets including bioassays, compounds that are of value as drug discovery tools and intellectual property.
In the first round of awards, made in November 2006, research on obesity, MRSA and cancer all received funding (see box, below). Two of the three recipients in the first round are university-based academic research teams. But the grants can also be awarded to commercial groups; indeed, one went to Prolysis Ltd, a venture-capital-backed company. Moreover, even large pharmaceutical companies could be partnered under the scheme if it led to research that would not otherwise be carried out, stresses Dr Davis. With the world in urgent need of new medicines, all kinds of novel collaborations will be needed.
1. Moran M et al. The new landscape of neglected disease drug development [PDF 830KB]. London: Wellcome Trust; 2005.
2. Moran M. A breakthrough in R&D for neglected diseases: new ways to get the drugs we need. PloS Med 2005;2(9):e302.
Seeding Drug Discovery
The first round of awards:
Professor Steve Bloom at Imperial College London for the development of a long-acting therapeutic agent to mimic our bodies' natural ability to control appetite.
Professor Jeremy Tavare's group at the University of Bristol for the development of optimising compounds to disrupt a signalling pathway implicated in cancer.
Prolysis Ltd for the development of new antibacterial drugs for MRSA-type infections.
Seeding Drug Discovery awards will be made twice a year over the next four years. The second round of awards will be made in May 2007.