Rockefeller scientists start testing glutamate-clearing drug in Alzheimer’s patients


As people get older, our genes wind down from the peak performance of youth. And reversing one of the genetic consequences of aging could point the way toward fighting Alzheimer’s and other cognitive ailments.

Using a drug called riluzole, which is sold by Sanofi ($SNY) as a treatment for ALS, investigators at Rockefeller University say they were able to restore expression of a gene called EAAT2 in an animal model, improving its ability to sweep away glutamate that can clog nerve fibers. Glutamate damages or eliminates neurons and is implicated in the memory-stealing disease that afflicts millions of people around the world, as well as cognitive declines in people as they age. .

"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, co-first author of the study published in Molecular Psychiatry, in a university news release. "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.”

Now Gray and Ana Pereira, an instructor in clinical medicine in Bruce McEwen's laboratory, are treating Alzheimer’s patients in a clinical study hosted by Rockefeller University Hospital.

"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," Pereira said in the release. "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.”

Aging has become a central focus in academic and some biotech circles in recent years. And while investigators have been concentrating their efforts on fighting individual diseases, the implication of their work extends to the broader work focused on changing the way people age, extending healthy life spans.

- here's the release
- get the journal abstract