Drug Can Potentially Reverse Cognitive Decline

Riluzole has been able to restore certain genes that impact cognitive function.

In a recent study, researchers found that the drug riluzole can reverse key genetic changes associated with Alzheimer’s disease and cognitive decline.

"In aging and Alzheimer's, the chemical signal glutamate can accumulate between neurons, damaging the circuitry," said lead researcher Ana Pereira, MD. "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."

As we age, glutamate, which is released to excite other neurons, can build up in intercellular spaces. According to a study published in Molecular Psychiatry, this happens when neurons make less of the transporter molecule responsible for removing excess glutamate.

When glutamate accumulates, the neurotransmitter can damage or kill neurons, which contributes to Alzheimer’s disease and other cognitive 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 researcher Jason Gray, PhD. "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."

Researchers found that the drug is able to modify the activity of certain genes in an older rat to resemble a younger one.

Researchers also found that the expression of EAAT2, a gene linked to Alzheimer’s that plays a role in removing excess glutamate from nerve fibers, decreases as an animal ages.

However, rats treated with riluzole had the gene’s activity brought back to levels seen in younger rats.

This drug is currently being used to treat amytrophic lateral sclerosis and is considered relatively safe.

"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," Dr Pereira concluded. "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 aging and even more significantly in Alzheimer's disease."