Riluzole and tirasemtiv — two drugs with connections to other neuromuscular disorders — are being tested as potential treatments for spinal muscular atrophy
In the search for therapies for spinal muscular atrophy (SMA), researchers are testing two drugs with connections to other neuromuscular disorders: riluzole, which is approved for use in amyotrophic lateral sclerosis (ALS); and tirasemtiv, which is already in testing for ALS and myasthenia gravis (MG).
|Editor’s note (May 31, 2013): This item was updated May 31, 2013, to reflect the fact that a clinical trial of riluzole in people with SMA has been completed in France.|
In experiments conducted in two different SMA research models, a team of researchers found that targeting "SK2" potassium channels with the ALS drug riluzole (brand name Rilutek), may be one possible approach to treating SMA. (Potassium channels are microscopic tunnels that make possible high-speed movement of electrically charged potassium ions across barriers inside cells and between cells and their surroundings.)
A deficiency of SMN protein underlies most SMA, and many of the strategies currently under development for the disease are based on increasing and maintaining SMN levels. In this case, however, the researchers found that treatment with riluzole actually decreased SMN levels; it appeared instead to work — at least in part — by activating SK2 potassium channels.
Working with a cellular model of SMA, researchers found that treatment with riluzole promoted the growth of axons, the long fibers that carry signals to and from nerve cells in the brain and spinal cord.
In another set of experiments, treatment with riluzole restored neuromuscular function and mobility in a worm model of SMA.
The research team published its findings April 10, 2013, in the Journal of Neuroscience. The full report is available, for a fee: The Neuroprotective Drug Riluzole Acts via Small Conductance Ca2+-Activated K+ Channels to Ameliorate Defects in Spinal Muscular Atrophy Models.
A phase 2-3 clinical trial to evaluate the efficacy of riluzole in children and young adults with SMA was conducted in France. No results have been reported.
Both SMA and ALS are classified as motor neuron diseases.
South San Francisco biopharmaceutical company Cytokinetics announced in an April 4, 2013, press release that it will begin conducting preclinical research aimed at determining whether its experimental compound tirasemtiv can improve muscle function in mouse models of SMA.
The company plans to examine the effects of tirasemtiv on leg and respiratory muscle function in the mice, and evaluate the potential for the drug to reduce fatigue and improve muscle strength during exercise.
Tirasemtiv — formerly known as CK-2017357 — is designed to increase the sensitivity of muscle fibers to calcium, thereby increasing skeletal muscle force in response to input from the nervous system, and decreasing muscle fatigue.
To learn more about the drug's mechanism of action:
Cytokinetics also is evaluating tirasemtiv for the treatment of ALS and MG. A phase 2b trial in ALS is under way, following encouraging results from earlier studies. Encouraging findings from a phase 2a clinical trial in MG were announced in a Nov. 26, 2012, press release.