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Collaboration to find a drug to treat CJD
Apr 12, 2005 - 11:04:00 PM
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The programme of work towards development of a candidate drug for potential trial in humans is estimated to take at least a further six years and the first phase of this work, which has followed a large scale initial pilot study will start soon. The UK Department of Health has agreed to fund the work through a grant award to the Institute of Neurology,UCL.
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By MRC, UK,
[RxPG] Today, an unprecedented collaboration between the UKs leading academic research group working on CJD the Medical Research Councils Prion Unit based at the Institute of Neurology, University College London and the UKs largest pharmaceutical company GlaxoSmithKline (GSK) - is announced.
The occurrence of variant Creutzfeldt-Jakob disease (vCJD) and the recognition that this is caused by exposure to the infectious agent or prion responsible for bovine spongiform encephalopathy (BSE) has led to fears of an epidemic of human infection with BSE prions - as many in the UK population will have been exposed to BSE prions prior to the introduction of rigorous controls to limit dietary exposure in 1996. Although the number of patients developing vCJD so far is thankfully relatively small (around 150), incubation periods for prion infections are known to span decades in humans and the number who may be silently infected and eventually develop disease is unknown, as are the numbers of secondary infections that may occur via contaminated blood products or surgical instruments. Because of these uncertainties, the development of an effective treatment to eradicate prion infection during the window of opportunity provided by the prolonged latent period of prion infection is considered a strategic priority. However, the rarity of CJD makes it an orphan disease which means normal commercial drug development is unrealistic.
A major effort has been underway for some years at the MRC Prion Unit to understand the fundamental and unique processes involved in the propagation of prions the remarkable infectious agents that cause CJD in humans and BSE and scrapie in animals. Much of this laborious and long term work has been to identify and validate the best target against which to develop a drug to block prions replicating. Prions are misfolded or rogue forms of one of the bodys own protein molecules the prion protein and the Unit has shown in prion-infected laboratory animals that the disease process in the brain can be halted by targeting this protein, without apparent deleterious effects. The aim is now to develop a drug that is capable of readily entering the brain and binding to the normal prion protein blocking the change in shape involved in it turning into the rogue prion.
To do this requires screening literally hundreds of thousands of potential drug-like molecules from large compound collections or libraries. One of the largest and best characterised such libraries in existence is that of GSK which contains over a million such compounds. Such libraries form one of the most important commercial assets of any pharmaceutical company and making such a library available to an academic group in this way is unprecedented. Peter Machin, Senior Vice President Chemistry & Screening Sciences at GSK said:
We are delighted to provide our compound collection of high quality, drug-like molecules to accelerate the search for compounds that may prove useful in the treatment of CJD
The programme of work towards development of a candidate drug for potential trial in humans is estimated to take at least a further six years and the first phase of this work, which has followed a large scale initial pilot study will start soon. The UK Department of Health has agreed to fund the work through a grant award to the Institute of Neurology,UCL. The partnership now forged between GSK, the MRC Prion Unit,and UCL, brings together for the first time all the relevant expertise and resources to make such a development feasible and may act as a stimulus to such academic-industy collaborations in other areas of medicine.
Professor John Collinge, Director of the MRC Prion Unit and Head of the Dept.of Neurodegenerative Disease at the Institute of Neurology,UCL, said:
Many person years of very difficult work at the MRC have been invested to get to the stage where development of a drug to completely block prions appears realistic. My colleagues and I, at the Unit, are absolutely delighted at the opportunity now to translate these advances in laboratory research into real benefit for patients affected by these dreadful diseases
There is only so far we can take things on our own as academic scientists and, while there is no guarantee of success, now having the enormous resource and expertise of GSK with us is extremely exciting.
Publication:
Medical Research Council (MRC)
On the web:
www.mrc.ac.uk 
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Additional information about the news article
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The Medical Research Council (MRC) is a national organisation funded by the UK tax-payer. Its business is medical research aimed at improving human health; everyone stands to benefit from the outputs. The research it supports and the scientists it trains meet the needs of the health services, the pharmaceutical and other health-related industries and the academic world. MRC has funded work which has led to some of the most significant discoveries and achievements in medicine in the UK. About half of the MRCs expenditure of £450 million is invested in its 40 Institutes, Units and Centres. The remaining half goes in the form of grant support and training awards to individuals and teams in universities and medical schools. Web site at: http://www.mrc.ac.uk
The Institute of Neurology is a specialist postgraduate Institute of University College London. The Institute is closely associated in its work with the National Hospital for Neurology & Neurosurgery, and in combination they form a national and international centre at Queen Square for teaching, training and research in neurology and allied clinical and basic sciences. Website at: http://www.ion.ucl.ac.uk
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