An experimental Alzheimer’s drug reverses changes in the brain that can trigger dementia, according to new research.
Ageing takes its toll on the brain, and the cells of the hippocampus - a region of the brain with circuitry crucial to learning and memory - are particularly vulnerable to changes that can lead to Alzheimer’s or cognitive decline.
With the hope of counteracting the changes that can lead to these two conditions, researchers have begun examining the effects of a drug known to affect the circuitry.
In new research, published in the journal Molecular Psychiatry, researchers described how the drug, riluzole, is capable of reversing key genetic changes associated with the conditions.
Study leader Doctor Ana Pereira, of Rockefeller University in the United States, said: “In ageing and Alzheimer’s, the chemical signal glutamate can accumulate between neurons, damaging the circuitry.
“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.”
Previous work by Dr Pereira’s team has shown the drug prompted structural changes in rats’ neurons that prevent the memory loss often seen in old animals.
Now Dr Pereira is currently testing riluzole for the first time in Alzheimer’s patients in a clinical trial at the Rockefeller University Hospital.
Dr Pereira and co-first author Doctor Jason Gray sought to better understand the molecular vulnerabilities of an ageing glutamate system and riluzole’s effect on it.
Dr Gray said: “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.
“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.”
The drug, it turns out, modifies the activity of certain genes in an aged animal to resemble that of a younger rat. For example, the 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.
But in rats treated with riluzole the gene’s activity was brought back to its youthful levels.
Dr Pereira said that, as well as its potential ability to allay memory loss and cognitive decline, riluzole is attractive as a potential treatment for Alzheimer’s. The drug is already being used to treat another neurological disease, amyotrophic lateral sclerosis, and is therefore considered relatively safe.
In Dr Pereira’s ongoing clinical trial, patients with Alzheimer’s have so far been treated with either the drug or a placebo, and have been undergoing tests to help determine whether their brain functions have been improved.
She 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.
“We found that, in addition to recovering the expression of EAAT2, the drug restored genes critical for neural communication and plasticity, both of which decline with ageing and even more significantly in Alzheimer’s disease.”