Scientists on verge of Alzheimer's memory loss 'breakthrough'

Scientists may have discovered a way to block Alzheimer's from causing memory loss in a development that could spell the end for families watching their loved ones condition deteriorate.

Scientists carried out Alzheimer's testing on mice.

The medical breakthrough, which so far has only worked in mice, involves removing a protein called Ephexin5 which prevents animals from developing the characteristic memory loss and improves thinking.

In the report published online in The Journal of Clinical Investigation, the researchers say the findings could eventually advance development of drugs that target Ephexin5 to prevent or treat symptoms of the disorder in humans.

Gabrielle Sell, a graduate student at Johns Hopkins University School of Medicine, said: “Ephexin5 is a tantalising pharmaceutical target because in otherwise healthy adults, there’s very little present in the brain.

“That means shutting off Ephexin5 should carry very few side effects.”

Their work with Ephexin5 grew from Alzheimer’s disease’s defining features, the development of thick plaques in the brain composed of a protein called amyloid beta.

Stemming the production of this protein is currently the major focus of efforts to develop new Alzheimer’s treatments, but it isn’t the amount of amyloid beta in patients’ brains that correlates best with the severity of symptoms; rather, it’s the loss of so-called synapses, a type of cellular structure forged between two brain cells.

Neuroscientist Dr Margolis discovered that when they added amyloid beta to healthy mouse brain cells growing in petri dishes, these cells began overproducing Ephexin5.

Additionally, when they injected the brains of healthy mice with amyloid beta, cells there also began overproducing Ephexin5 - both clues that the protein that makes Alzheimer’s characteristic plaques appears to trigger an increase in brain cells’ production of Ephexin5.

When the researchers examined preserved brain tissues isolated from Alzheimer’s patients during autopsies, they also found similarly high levels of Ephexin5.

Armed with what they called this wealth of evidence that brain cells produce too much Ephexin5 when Alzheimer’s disease linked to amyloid beta is present, the researchers then investigated whether reducing Ephexin5 might prevent Alzheimer’s deficits.

Using genetic engineering techniques that knocked out the gene that makes Ephexin5, the researchers developed mouse Alzheimer’s disease models whose brain cells could not produce the protein.

Although the animals still developed the characteristic Alzheimer’s amyloid plaques, they did not lose their memory.

Dr Rosa Sancho, Head of Research at Alzheimer’s Research UK, said: “The loss of connections between nerve cells is a key feature of Alzheimer’s, and one that is being increasingly recognised by those searching for potential new medicines for the disease. This study has revealed a new player controlling nerve cell communication that could be contributing to Alzheimer’s. These are important early steps along the road to new treatments for Alzheimer’s, and future studies will need to explore whether it is possible to safely reduce the levels of exphexin5 in the brain as an approach to help those living with Alzheimer’s. With 850,000 people in the UK living with dementia, it’s vital that research continues to develop effective new treatments for those affected and their families.”

It is hoped the results on mice will transfer to humans.

Neuroscientist Dr Seth Margolis cautions that while the results all suggest removing Ephexin5 prevented Alzheimer’s disease-associated impairments, they don’t on their own provide a true test for the approach to treatment.

That’s because in people with Alzheimer’s disease, the brain is exposed to amyloid beta for some time, probably decades, before any treatments might be administered.

The team is currently investigating whether drugs currently in clinical trials for Alzheimer’s disease could be exerting effects on Ephexin5 and how brain cells naturally regulate Ephexin5.