Researchers at Brown University and Boston Children’s Hospital have identified a new potential mechanism for developing a treatment for spinal muscular atrophy (SMA). The research, published in the Journal of Neuroscience, reports that the ALS drug Riluzole advanced neural cell development in a mammalian model of SMA and restored neuromuscular function and mobility in a Caenorhabditis elegans worm model of the disease.
Riluzole has already been tested as a therapy in a very small study of severely affected SMA patients. It failed to help. Nevertheless, what makes the new research encouraging, said Anne Hart, professor of neuroscience at Brown and senior author on the paper, is that the study traces the beneficial action of Riluzole to specific “SK2” potassium channels in worm neurons. Humans have these channels too, and if they can be more precisely targeted by a new drug, she said, that could make a more meaningful difference, at least for some patients.
“We’re not suggesting based on this that SMA patients should ask their doctors for Riluzole,” Hart said, “but we are suggesting that this pathway would be useful for therapeutic development.”
In the mammalian neuronal cells, the Children’s Hospital researchers found that Riluzole promoted the growth of axons that was lacking in the SMN-depleted cells. However, Riluzole did this not by increasing SMN levels. Instead, the researchers found evidence that drug treatment matured the neurons more quickly in normal cells.
Most attempts to treat SMA have relied on trying to maintain or restore higher levels of SMN, Hart noted. But Riluzole, or a future drug, may instead be able to work by accelerating cell maturity.
Riluzole has already been tested as a therapy in a very small study of severely affected SMA patients. It failed to help. Nevertheless, what makes the new research encouraging, said Anne Hart, professor of neuroscience at Brown and senior author on the paper, is that the study traces the beneficial action of Riluzole to specific “SK2” potassium channels in worm neurons. Humans have these channels too, and if they can be more precisely targeted by a new drug, she said, that could make a more meaningful difference, at least for some patients.
“We’re not suggesting based on this that SMA patients should ask their doctors for Riluzole,” Hart said, “but we are suggesting that this pathway would be useful for therapeutic development.”
In the mammalian neuronal cells, the Children’s Hospital researchers found that Riluzole promoted the growth of axons that was lacking in the SMN-depleted cells. However, Riluzole did this not by increasing SMN levels. Instead, the researchers found evidence that drug treatment matured the neurons more quickly in normal cells.
Most attempts to treat SMA have relied on trying to maintain or restore higher levels of SMN, Hart noted. But Riluzole, or a future drug, may instead be able to work by accelerating cell maturity.
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