Riluzole is an approved oral medication to slow disease progression in amyotrophic lateral sclerosis (ALS). Researchers at The Rockefeller University are now investigating whether riluzole might also be effective in treating cognitive problems linked to Alzheimer’s disease.

How riluzole works

The exact cause of Alzheimer’s is unknown, but the disease damages and kills brain cells and it is thought that this may be caused by the abnormal accumulation of proteins called beta-amyloid and tau. Scientists also suspect that some of the damage caused by Alzheimer’s and by aging, in general, is due to the accumulation of glutamate.

Glutamate is a neurotransmitter, or signaling molecule, that carries information between nerve cells. Normally it is reabsorbed quickly and does not build up between brain cells, but in aging brains and brains affected by Alzheimer’s disease, glutamate is not reabsorbed efficiently and can accumulate. This excess glutamate can damage or even kill brain cells.

Riluzole increases the activity of a gene called EAAT2, which contains instructions for a protein that enables brain cells to reabsorb glutamate.

In rats, riluzole reversed some of the gene activity changes seen in Alzheimer’s disease and improved the rats’ memory performance. It also restored the gene activity needed for neural communication and plasticity that declines in Alzheimer’s.

Riluzole in clinical trials for Alzheimer’s

Because riluzole is already approved by the U.S. Food and Drug Administration (FDA) as an ALS treatment, its safety and tolerability have already been evaluated. Therefore, researchers are starting with a small Phase 2 clinical trial (NCT01703117) to evaluate riluzole as a treatment for mild Alzheimer’s disease.

This one-site study (Rockefeller University in New York) is recruiting about 48 people ages 60 to 85 and diagnosed with mild Alzheimer’s, who are currently taking a cholinesterase inhibitor. The study will run for approximately six months and participants will either receive oral riluzole or a placebo. Tests of cognitive function, as well as brain imaging, will be used to evaluate the treatment’s effectiveness. The study is expected to conclude in November of 2020.

A “prodrug” of riluzole, called troriluzole (BHV-4157), is also being investigated as a possible treatment for Alzheimer’s disease. A “prodrug” means that troriluzole is converted to riluzole by the body after it is ingested. In July of 2017, Biohaven and the Alzheimer’s Disease Cooperative Study (ADCS) initiated a Phase 2 clinical trial to evaluate troriluzole as a treatment for Alzheimer’s disease. The trial is called T2 Protect AD (NCT03605667) and will recruit 292 patients with mild to moderate Alzheimer’s disease at 44 sites across the United States.  The patients will be given either oral troriluzole or a placebo for 48 weeks at which point their scores on the Alzheimer’s Disease Assessment Scale Cognitive Subscale (ADAS-Cog 11) will be compared to baseline values to see how much of a decline there was. The trial is estimated to finish in February of 2020.


Last updated: Sept. 9, 2019


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