Alzheimer’s to Benefit from Landmark MRC-AstraZeneca Compound Collaboration

The MRC has announced funding of £7 million for 15 research projects awarded through its ground-breaking collaboration with innovative pharmaceutical company AstraZeneca, which gave academic researchers unprecedented access to 22 chemical compounds.

The researchers led by Seth Love, Professor of Neuropathology in the School of Clinical Sciences, will investigate whether a compound originally evaluated by AstraZeneca for the treatment of prostate cancer could delay, or even reverse, the progression of Alzheimer’s disease by improving blood flow through the brain.

Alzheimer’s is the most common form of dementia. It is thought to affect around half a million people in the UK and its occurrence in the population is on the rise. It occurs when protein plaques and tangles develop in the brain, damaging the nerve cells. No-one knows exactly what causes the disease, in which there is build-up of a protein called amyloid beta (Abeta) in the brain.

Professor Love and his colleagues have been investigating why blood flow through the brain is reduced in people with Alzheimer’s. The more severe this reduction, the worse their symptoms and the more rapidly the disease progresses. In recent studies the group has found that the Abeta causes cells in the brain to overproduce enzymes that act on blood vessels in the brain and cause them to narrow.

By blocking the action of these enzymes, the scientists hope they can restore blood flow to the brain and improve cognitive function (or at least slow the decline). This is a completely new approach to treating Alzheimer’s as most people are currently treated with drugs that increase levels of chemical messengers known as neurotransmitters in the brain.

This Bristol-based collaborative study will test the AstraZeneca compound (zibotentan), and another drug (losartan) developed to treat high blood pressure, to assess whether they are capable of blocking the effects of Abeta on brain blood flow. If successful, the researchers hope to secure funds to carry out a randomised controlled trial in patients with Alzheimer’s disease to see whether zibotentan can halt or slow the dementia and improve their quality of life.

Professor Love said: “We were delighted to have the chance to collaborate with AstraZeneca on such an exciting project. We now have a great opportunity to test a fundamentally new approach to Alzheimer’s treatment that if successful could be rapidly translated into the clinic.”

The MRC-AstraZeneca compound collaboration was first announced by Prime Minister David Cameron in December 2011 as part of the UK Life Sciences Strategy.

AstraZeneca made 22 of its chemical compounds available free-of-charge to scientists, who were encouraged to apply for MRC funding to use them in medical research with the ultimate aim of benefitting patients. AstraZeneca had conducted early trials of these compounds and validated their use for future research, but had put them on hold for further development.  This collaboration extends the possible application of these compounds for use in new areas.

Professor Patrick Johnston, Chair of the MRC’s Translational Research Group, said: “The quality of applications we received for the MRC-AstraZeneca collaboration was higher than we could ever have hoped and we are delighted to be funding 15 excellent projects. Thanks to the generosity of AstraZeneca, UK scientists will be able to carry out medical research that otherwise may never have been possible. Not only will this bring benefits for patients in the form of more effective medicines and a better understanding of disease, but it has also allowed academic researchers to forge new partnerships with industry, which will give rise to future collaboration across the life sciences sector.”

Martin Mackay, President of AstraZeneca Research and Development, said: “AstraZeneca strives to realise the full potential of its portfolio by collaborating with research experts worldwide in our search for new and effective medicines that can benefit patients. Partnering across government, academia and industry is a critical way to spur additional scientific innovation and the delivery of new treatments for people who desperately need them.”

David Willetts, Minister for Universities and Science, said: “This landmark collaboration will see our leading scientists working with industry to find new insights into disease. It will speed up the search for innovative treatments and keep the UK at the forefront of biomedical research, which will in turn drive growth and deliver benefits for patients.”

Sharmila Nebhrajani, Chief Executive of the Association of Medical Research Charities said: “From serious but common conditions such as Alzheimer’s to rarer diseases including motor neurone disease and muscular dystrophy, we still have only a limited understanding of the way diseases develop and few therapies available for patients. Scientific advance is rooted in collaboration. The £7 million funding announced today allows scientists access to previously unavailable compounds that may hold the key to understanding some highly debilitating diseases. Patients are anxiously waiting for new therapies, and collaborations that speed up the time it takes for medicines to be developed and become available to the public are especially welcome. Medical research charities, which themselves invest over £1 billion in scientific research each year and have dedicated patient supporters, are also keen to pool our resources with industry and public funders to maximise the impact of this investment.”

After looking at over 100 expressions of interest, the MRC received 23 full funding proposals. The applications were assessed by the MRC, independently of AstraZeneca through international expert peer review, and the 15 successful proposals were selected on the basis of scientific quality and importance.

The rights to intellectual property (IP) generated using the compounds will vary from project to project, but will be equitable and similar to those currently used in academically-led research. AstraZeneca will retain its existing rights relating to the compounds and any new research findings by the academic institution will be owned by the academic institution.