Injections of Melatonin Delay Symptom Onset and Death in ALS Mouse Model

ALS is the most common motor neuron disease, affecting more than 86,000 people worldwide with an average life expectancy of only three to five years from onset.

Investigators at the University of Pittsburgh School of Medicine (PA, USA) identified melatonin as a potential drug for ALS therapy when it a gave positive result during a study that screened more than a thousand FDA-approved drugs for compounds capable of inhibiting cytochrome c release in purified mitochondria and preventing cell death in cultured neurons.

In follow up experiments, the investigators evaluated whether melatonin would slow disease progression in SOD1G93A mice. The mutant SOD1G93A transgenic mouse ALS model demonstrates the pathogenesis of motor neuron degeneration due to caspase-mediated cell death combined with other factors such as inflammation and oxidative damage.

The investigators reported in the July 2013 online edition of the journal Neurobiology of Disease that melatonin significantly delayed disease onset, neurological deterioration, and mortality in ALS mice. They determined that disease progression was associated with the loss of both melatonin and the melatonin receptor 1A (MT1) in the spinal cord of ALS mice.

"Our experiments show for the first time that a lack of melatonin and melatonin receptor 1, or MT1, is associated with the progression of ALS," said senior author Dr. Robert Friedlander, professor of neurosurgery and neurobiology at the University of Pittsburgh School of Medicine. "We saw similar results in a Huntington's disease model in an earlier project, suggesting similar biochemical pathways are disrupted in these challenging neurologic diseases. Much more work has to be done to unravel these mechanisms before human trials of melatonin or a drug akin to it can be conducted to determine its usefulness as an ALS treatment. I suspect that a combination of agents that act on these pathways will be needed to make headway with this devastating disease."

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