This is a cross-post from the Blogging for Science Online London group blog. During the Saturday workshop at Science Online London 2011, a bunch of us wrote content relating to Spinal Muscular Atrophy. My post was a short summary of a small scale drug trial, which shows promising results.
This is a summary of a paper that shows that Salbutamol promotes SMN2 expression in vivo [cite]10.1136/jmg.2010.080366[/cite].
Patients with Spinal Muscular Atrophy (SMA) have no functioning copy of the gene SMN1. The SMN2 gene can theoretically function in its place, but a change in this gene means that only a small amount of functional protein is produced from the gene.
It is therefore suggested that any intervention that can increase the level of functional SMN2 transcript could well be effective as a treatment for SMA.
Salbutamol is a short acting beta-adrenergic agonist that is primarily used for treating asthma. A previous study [cite]10.1136/jmg.2007.051177[/cite] has shown that Salbutamol is effective in raising SMN2 full length (SMN2-fl) levels in cultured SMA fibroblasts.
In this study, the researchers administered Salbutamol to 12 patients with SMA, and measured the levels of SMN2-fl 3 times (0, 3 and 6 months). The levels of SMN2-fl were significantly increased in all but 3 patients after 3 months (average increase of 48.9%), and in all patients after 6 months (average increase of 91.8%). They also showed that patients with more copies of the SMN2 gene (some patients had 3 copies, some had 4) showed a larger response to Salbutamol treatment. This increase in expression cannot be explained by normal fluctuations over time in these patients, since studies have shown that levels of SMN2-fl are usually stable over time [cite]10.1212/01.wnl.0000252934.70676.ab[/cite] [cite]10.1038/ejhg.2009.116[/cite]. Clearly the big question now is whether this molecular response to the drug is reflected in a beneficial clinical response in the patient. This study does not address this question, but does propose that a full double-blind, placebo controlled trial should be carried out to ascertain whether or not this treatment is effective in treating the symptoms of SMA.
Tiziano, F., Lomastro, R., Pinto, A., Messina, S., D’Amico, A., Fiori, S., Angelozzi, C., Pane, M., Mercuri, E., Bertini, E., Neri, G., & Brahe, C. (2010). Salbutamol increases survival motor neuron (SMN) transcript levels in leucocytes of spinal muscular atrophy (SMA) patients: relevance for clinical trial design Journal of Medical Genetics, 47 (12), 856-858 DOI: 10.1136/jmg.2010.080366