Alzheimer's potential for epilepsy drug
08 December 2008
A drug commonly used to treat epilepsy could help clear the plaques in the brain associated with Alzheimer’s disease. Researchers funded by the Medical Research Council have found that sodium valproate - which is marketed as the anti-seizure drug Epilim - reactivates the body’s own defences against a small protein called amyloid beta peptide, which is the main component of the brain plaques characteristic in Alzheimer’s. The plaques are known to lead to the progressive death of nerve cells in the brain linked to many forms of dementia.
The research, carried out at the University of Leeds, is published online in EMBO Reports.
Professor Tony Turner from the University’s Faculty of Biological Sciences said: “The fact that we’ve been able to show in the lab that a well-established, safe and relatively inexpensive drug has the potential to treat Alzheimer’s is an extremely exciting development. We hope colleagues will be able to progress this research with clinical trials in the near future.”
Alzheimer’s disease is the most common form of dementia and has no cure. In the UK today there are half-a-million people living with Alzheimer’s. This is expected to double within a generation unless new treatments are found.
Sodium valproate has been used for many years to suppress epileptic seizures and the many people with epilepsy have been taking the drug for decades with few side effects.
The development of Alzheimer’s is widely believed to be caused by the gradual accumulation in the brain of amyloid-beta peptide which is toxic to nerve cells. This is thought to be caused by a key enzyme called neprilysin or NEP gradually switching off in later life. One of NEP’s roles is to clear the toxic peptide from the brain, and plaques begin to form as it gradually switches off, leading to the death of the brain’s nerve cells.
The research team, including chromatin specialist Dr Nikolai Belyaev and neuroscientist Dr Natalia Nalivaeva, examined changes in chromatin – the ‘packaging’ that genes are contained within - and surmised that these changes might be involved in switching off NEP. The team found clear differences in chemical modifications (acetylation) to key proteins within the chromatin when they compared normal nerve cells against those that failed to produce NEP.
Professor Turner added: “From there it was relatively simple to stimulate the expression of NEP with sodium valproate which was seen to prevent the acetylation, in effect keeping NEP ‘switched on’. We were elated when we saw the results.”
Professor Tony Turner, together with former colleague Dr John Kenny, first discovered NEP in the brain.
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Reference:
Nikolai D. Belyaev, Natalia N. Nalivaeva, Natalia Z. Makova & Anthony J. Turner (2008) Neprilysin gene expression requires binding of the amyloid precursor protein intracellular domain to its promoter: implications for Alzheimer disease is published online in the European Molecular Biology Organization Reports (EMBO Reports).
