A drug designed for diabetes sufferers could have the potential to treat neurodegenerative diseases like Alzheimer’s, a study by scientists at the University of Ulster has revealed. In research revealed in the Sept. 14 issue of the Elsevier journal Brain Research a drug which was originally designed to target Type II diabetes, may in fact have greater application for keeping brain cells healthy and preventing Alzheimer’s disease.
Type II diabetes is a known risk factor for Alzheimer’s and in fact, Alzheimer’s has been termed Type III diabetes by some researchers. It is thought that impaired insulin signalling in the brain may damage nerve cells, contributing significantly to the disease process.
The neurodegeneration that occurs in Alzheimer’s disease is consistently linked to a number of specific changes in the anatomy, biochemistry and molecular structure of the brain, most commonly the neurofibrillary tangles, malformed nerve cells and deposits of a sticky protein called amyloid-?. There is also evidence of chronic oxidative stress on the brain tissue, impaired energy metabolism and mitochondrial function and an increase in the activation of genes and signalling pathways which cause cell death, ordinarily a healthy process in the body which prevents cells from becoming cancerous. A major problem in accurately diagnosing Alzheimer’s disease, however, is that these changes cannot be definitively seen until after the patient has died, at autopsy.
Since 2005, when it was discovered that insulin was not only produced in the pancreas, but also in the brain, there has been an increasing body of evidence that impaired glucose utilization by the brain, and other abnormal energy metabolism factors, play a key role early in the disease. It has been hypothesized that correcting deficiencies in the insulin signalling pathways in the brain may help to slow the progression of Alzheimer’s disease, preserving mental function for longer.
Prof Christian Hölscher and his team at the Biomedical Sciences Research Institute treated healthy mice with an experimental drug called (Val8)GLP-1, which mimics the activity of a protein (called GLP-1) which helps control the response to blood sugar. Prof. Holscher then studied the effect of the drug on the brain with surprising results.
Prof Hölscher, said: “Here at the Biomedical Sciences Research Institute, we are really interested in the potential of diabetes drugs for protecting brain cells from damage and even promoting new brain cells to grow. This could have huge implications for diseases like Alzheimer’s or Parkinson’s, where brain cells are lost.
“It is very encouraging that the experimental drug we tested, (Val8)GLP-1, entered the brain and our work suggests that GLP-1 could be a really important target for boosting memory. While we didn’t see benefits on learning and memory in these healthy mice, we are keen to test the drugs in mice with signs of Alzheimer’s disease, where we could see real improvements.”
Very few substances are capable of crossing from the blood stream into the brain, a protective mechanism to ensure our most valuable organ is kept safe from the myriad of substances in our environment which may cause it harm. The experimental drug, however, was capable of crossing the blood-brain barrier or BBB and, at the doses tested, did not appear to cause any side-effects.
The drug was found to have promoted new brain cells to grow in the hippocampus region of the brain, an area known to be involved in memory processes. This suggests that, as well as its role in insulin signalling, the protein GLP-1 may also be an important part of the production of new nerve cells. When the researchers blocked the effect of GLP-1 in the brain, the mice performed poorly on learning and memory tasks. Boosting the effect of GLP-1 did not appear to have any effect on the behaviour of the mice.
The research has been funded by Alzheimer’s Research UK, the leading dementia research charity in the United Kingdom.
Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, said:
“We are pleased to have supported this early stage research, suggesting that this experimental diabetes drug could also promote the growth of new brain cells. While we know losing brain cells is a key feature of Alzheimer’s, there is a long way to go before we would know whether this drug could benefit people with the disease.
“This research will help us understand the factors that keep nerve cells healthy, knowledge that could hold vital clues to tackling Alzheimer’s. With over half a million people in the UK living with the disease, learning more about how to keep our brain cells healthy is of vital importance. Funding for dementia research lags far behind that of other common diseases, but is essential if we are to realise the true potential of research like this.”
Stephen F.J. McGovern, Kerry Hunter, Christian Hölscher.Effects of the glucagon-like polypeptide-1 analogue (Val8)GLP-1 on learning, progenitor cell proliferation and neurogenesis in the C57B/16 mouse brain. Brain Research, 2012; 1473: 204 DOI:10.1016/j.brainres.2012.07.029
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