University of Dundee University of Dundee
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23 November 2010

Dundee researchers and European collaborators find that anti-diabetes drug fights Alzheimer's

A potentially exciting breakthrough in the treatment and prevention of Alzheimer's disease has been made by researchers at the University of Dundee and their international collaborators.

They have discovered that metformin, a drug commonly used in the treatment of Type II Diabetes, can help treat Alzheimer’s disease (AD) and also prevent it in healthy people.

A paper published in the most recent edition of Proceedings of the National Academy of Sciences of the United States of America, known as PNAS, shows that metformin has a significant influence on one of the key causes of the development of AD.

It has long been known that sugar metabolism is a critical factor in the development of AD, and that patients with Diabetes have a higher risk for AD than those who are non-diabetic. The team from Dundee showed that metformin significantly activates a key protein which can prevent cell death in the brains of AD patients.

The risk of Alzheimer’s increases with age and reaches up to 50 per cent in those over 90 years old. Patients lose orientation relatively quickly and require a high level of care, creating an extraordinary challenge for relatives and public health systems. No effective cure has yet been discovered.

Susann Schweiger, Professor of Molecular Medicine at the University's Division of Medical Sciences, led the research. She explained that the idea to explore metforimin as a possible means of treating and preventing Alzheimer’s occurred to her out of the blue.

'I knew about the effects that metformin had in Type II Diabetes,' she said. 'I was cycling to work one day and it occurred to me that if metformin can work in Type II Diabetes and given its mode of function, then it should also have beneficial effects in Alzheimer's disease.

'I was able to put together an excellent team here in Dundee, as well as working with international colleagues, and our results strongly suggest that, not only in Type II Diabetes patients but also in healthy people, metformin would have a brain-protective effect and that, if given in an early stage, would be a promising medication in the treatment of Alzheimer's.

'The implications of this research are that, because metformin is already often used in clinical practice, it could go into a clinical trial with Alzheimer’s patients soon. We have shown how the drug works in the brain and the pathology, we would assume, is the same in people who are not diabetic but who have developed Alzheimer's.

'We would envisage this treatment being used after an early-stage diagnosis of Alzheimer’s. We are not expecting to revive cells that are already dead, but to protect those not yet damaged by the progression of Alzheimer's.

'The team will now apply for funding for a large, pre-clinical, trial into two different types of Alzheimer’s models. We will also further examine the biochemical processes to see how metformin affects the brain. Pretty soon we would hope to move towards a full clinical trial in AD patients.

'We already know that metformin has few side effects as it is widely used in elderly patients who will be the most likely recipients of this treatment, meaning we already know about safe dosage and usage.'

Professor Schweiger's team included Paul Thornhill, John Sharkey, Ritchie Williamson, Calum Sutherland from the Biomedical Research Institute, part of the University’s School of Medicine and located at Ninewells Hospital. Désirée Rutschow and Raphael Zeller of the Division of Medical Sciences also contributed to the research, as did collaborators from Austria and Germany.

Notes for Editors:

Of the 700,000 people with dementia in the UK, around 400,000 have Alzheimer's disease. Alzheimer's disease is named after Dr. Alois Alzheimer who first identified the disease in a patient in Germany in 1906. It is an irreversible, progressive brain disorder which causes dementia; the loss of cognitive functioning such as reasoning, thinking, remembering. Most sufferers have 'late onset' Alzheimer's, where symptoms appear after age 60; in some families, 'early-onset' familial cases can be caused by gene mutation in their thirties, forties or fifties. The trigger for the Alzheimer's disease process is not clear, but it is known that damage to the brain can begin up to 20 years before the symptoms become evident.

First published in 1915, The Proceedings of the National Academy of Sciences of the United States of America, known as PNAS, is the official journal of the United States National Academy of Sciences. It is the second most cited scientific journal in the world with 1,338,191 citations from 1994-2004 and anImpact Factor 9.432 of 2009, and11.6 million hits every month.

The article is entitled: ‘The Biguanidemetformin acts on tauphosphorylation via mTOR/PP2vAsignalling’, by Eva Kickstein, Sybille Krauss, Paul Thornhill, Désirée Rutschow, Raphael Zeller, John Sharkey, Ritchie Williamson, Melanie Fuchs, Andrea Köhler, Hartmut Glossmann, Rainer Schneider, Calum Sutherlandv & Susann Schweiger

Susann Schweiger (MD)
Professor of Molecular Medicine
Division of Medical Sciences
Ninewells Hospital & Medical School
University of Dundee
DD1 9SY Dundee
T: +44 1382 496235
Mobile: 07772627721
F: +44 1382633952

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