Wellcome Trust backs epigenetics project
pharmafile | January 13, 2009 | News story | Research and Development |Â Â epigeneticsÂ
A public-private partnership aiming to determine the three-dimensional structure of medically-relevant proteins and put them in the public domain has won a major grant from the Wellcome Trust.
The UK medical charity has set aside £4.1 million ($6.3m) for the initiative, which is being held up as a new model for R&D interactions between academia and industry as it places compounds in the public domain much earlier than usual.
Led by the non-profit Structural Genomics Consortium (SGC), the project aims to develop small-molecule inhibitors for 25 proteins thought to be involved in epigenetic signalling – a phenomenon in which genes can change behaviour without any alteration in DNA sequence.
This type of signalling involves chemical modifications of DNA or proteins that affect their function. For example, a gene can be passed from parent to offspring with an identical nucleic acid sequence, but still express protein at different rates or times, depending on the environment in the cell.
The hope is that, through the use of chemical probes that can block or stimulate the activity of a protein, researchers will be able to explore how epigenetic factors affect a number of illnesses, including cancer, diabetes, obesity and Alzheimer's disease.
It is anticipated that the probes would be used alongside other tools, such as 'silencing' genes through the use of RNA interference and genetic knockout models. Some probes may turn out be starting points for new directions in drug discovery.
Johan Weigelt, associate director of the SGC and based at the Karolinska Institute in Sweden, told Pharmafocus that the lack of high-quality chemical probes has been a major bottleneck in drug discovery.
"At the moment, around nine out of 10 compounds that enter the clinic fail because of efficacy, safety or toxicology issues," he said. "And the main reason for that is we simply don't understand the biology of the diseases we are trying to treat."
The SGC's aim is to develop, characterise and then disseminate the structure and function of each of the probes. And it is here that the approach diverges from traditional partnerships between pharma and academic institutions.
"Pharmaceutical companies have traditionally kept information about their probes in-house until a drug development project is well advanced or completed," explained Weigelt.
Aside from concerns about competition and the race to bring new drugs to market, the reasoning was also that going public on an inhibitor could in fact hamper further research in the area by the wider pharmaceutical sector.
However, Weigelt believes that companies will benefit from having teams of academic researchers identifying and validating new disease targets.
The Wellcome Trust agrees. "History shows that the pharmaceutical industry is far more likely to pursue a drug discovery programme if there are already well-characterised inhibitors with defined mechanisms of action available," said the charity in a statement.
The SGC will work alongside other groups in the project, notably GlaxoSmithKline, which will provide medical chemistry expertise, and the US National Institutes of Health Chemical Genomics Center (NCGC), which will carry out functions such as assay development and high-throughput screening.
