Drug may reverse genetic changes behind Alzheimer's

A drug which is already being used to treat a neurological disorder may also be able to reverse genetic changes behind Alzheimer's disease, a new study has claimed.
Ageing takes its toll on the brain, and the cells of the hippocampus - a brain region with circuitry crucial to learning and memory - are particularly vulnerable to changes that can lead to Alzheimer's disease or cognitive decline.
The drug, riluzole, is capable of reversing key genetic changes associated with these conditions, researchers said.
"In ageing and Alzheimer's, the chemical signal glutamate can accumulate between neurons, damaging the circuitry," said Ana Pereira from Rockfeller University in the US.

"When we treated rats with riluzole, we saw a suite of changes. Perhaps most significantly, expression of molecules responsible for clearing excess glutamate returned to more youthful levels," said Pereira.
Generally, glutamate is released to excite other neurons and does not linger in the spaces between them.

As we age, though, the system gets a little leaky and glutamate can build up in these intercellular spaces, researchers said.
This happens in part when neurons make less and less of the transporter molecule responsible for removing excess glutamate, they said.
When it accumulates, this essential neurotransmitter can cause big problems, damaging or killing neurons and so contributing to Alzheimer's disease, and other disorders.

"The essence is we used a drug known to modulate glutamate, and when we gave it to old rats, we saw it reversed many of the changes that begin in middle age in the hippocampus," said Jason Gray from Rockfeller University.
"We saw a similar pattern when we compared the riluzole-induced changes to data from Alzheimer's patients - in a number of key pathways in the hippocampus, the drug produced an effect opposing that of the disease," said Gray.
The drug modifies the activity of certain genes in an aged animal to resemble that of a younger rat.
For example, researchers found that the expression of a gene called EAAT2, which has been linked to Alzheimer's and is known to play a role in removing excess glutamate from nerve fibres, declines as the animals age.

However, in rats treated with riluzole, this gene's activity was brought back to its youthful levels.
In addition to its potential ability to allay memory loss and cognitive decline, riluzole is attractive as a potential treatment for Alzheimer's, researchers said.
The drug is already being used to treat another neurological disease, amyotrophic lateral sclerosis, and is therefore considered relatively safe, researchers said.
"We hope to use a medication to break the cycle of toxicity by which glutamate can damage the neurons that use it as a neurotransmitter, and our studies so far suggest that riluzole may be able to accomplish this," said Pereira.

The findings were published in the journal Molecular Psychiatry.