Glutamate Research Could Lead to ALS Treatment

Decades of research on the neurotransmitter glutamate have produced promising results that could lead to treatment for Amyotrophic Lateral Sclerosis (ALS).  Scientists believe excessive exposure to glutamate may be one of the reasons that nerve cells (motor neurons) die in ALS.  Preventing the rise of glutamate levels could be the key to protecting motor neurons and impeding the progress of the disease. 

Many attempts have been made to find therapy that would reduce glutamate injury.  Although Riluzole, --the only approved drug for ALS treatment—is believed to regulate the glutamate system, the therapeutic benefits of this drug are modest.  As a result, scientists are developing ways to quickly test the effectiveness of other drugs against ALS. 

The ALS Association partnered with the National Institutes of Neurological Disorders and Stroke to screen a series of potential drugs.  From this initiative, researchers demonstrated that Ceftriaxone helped mice live longer, and initiated a clinical trial for this drug.  

Albeit an exciting finding in mice, it remains to be seen whether Ceftriaxone works in patients.  The search continues for drugs that fight ALS.  Though too much glutamate can be toxic, normal levels of glutamate are necessary for the nervous system to function properly.  Scientists are cautious to select a drug that would clear the excess glutamate while maintaining normal glutamate levels.  

Scientists at Johns Hopkins University and Columbia University Medical Center have shown that Ceftriaxone works in mice by keeping glutamate levels in check.  Ceftriaxone increases levels of EAAT2, a cellular component that removes excess glutamate before it can build up and damage motor neurons.

Researchers at the Ohio State University and Harvard Medical School screened approximately 140,000 compounds and confirmed that 61 of them increased EAAT2 levels in cells.  This study has provided an excellent starting point for finding drugs that protect motor neurons from excessive glutamate exposure.

Learning more about the glutamate system will help scientists enhance their knowledge of ALS.  However, many factors are involved in the biology of ALS, and it is unclear whether any drug that specifically targets the glutamate system will be the most effective way of treating the disease. 

Despite the challenges, scientists believe the progress in glutamate research is cause for optimism and could lead to treatment for ALS.

Revised March, 2011

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