Long-Term Assessment of Salbutamol in SMA Type 3

10 April 2019

This latest article comes from our Clinical Care Research Correspondent, Dr Alex Murphy:

Summary

Tiziano and colleagues looked at individuals with SMA taking salbutamol over a one year period1. They were interested in trying to assess whether salbutamol was safe, whether it had the expected effect, and whether there was a significant effect on muscle function. This article summarises their findings.

Main text

Salbutamol is one of the few medications which has shown some evidence of a positive effect in individuals with SMA. Salbutamol in SMA is thought to increase SMN2 levels, which may in turn increase SMN and lead to a reduction in symptoms of SMA. Although it was considered for inclusion within the recent update of the standards of care for SMA, there was insufficient evidence to support recommended use for all individuals with SMA. Currently there are no widespread recommendations of salbutamol usage in SMA, and there is a lot of variation in practice.

Tiziano and colleagues looked at individuals with SMA Type 3 over a period of a year1. They included 45 participants in their study, with 23 receiving salbutamol and 22 receiving a placebo. Participants returned for blood tests and clinical assessments at four points throughout the year-long follow up.

Salbutamol was said to be well tolerated, with few side effects. The main reported issues were increased tremor (shaking of the hands), fast heart rate, and cramping pain. No treatment was required for any of these side effects. Blood tests showed that a muscle enzyme (creatine kinase) significantly increased in the group taking salbutamol, which the authors state has been seen previously with this type of medication, and didn’t cause any medical problems.

Tiziano and colleagues found that there was an increase in the levels of messages coming from SMN2 (mRNA transcripts), which in theory may lead to an increase in SMN protein levels. However, these findings did not reach significance; meaning that the study is unable to show an increase in SMN2 levels in the salbutamol group compared to the placebo group.

The authors also looked at whether the group receiving salbutamol were significantly better on measurement of muscle function and ambulation, such as the six minute walk test (how far a participant can walk in six minutes on the flat, as assessed by a physiotherapist). The results did demonstrate a significant difference between the groups, with participants receiving salbutamol able to walk an extra 20.5m on average, and a higher North Star Ambulatory assessment score (physiotherapy assessment tool designed to test how well muscles can perform movements important in daily life). The authors said that all salbutamol treated participants expressed a subjective reduction in their weakness due to a perceived reduction in their fatiguability.

Conclusions

Tiziano and colleagues have used a strong type of study design to look at a medication which has not been studied in a great deal of detail. The study failed to show a significant increase in SMN levels in response to treatment, although they did show a small improvement in muscle function (measured by a physiotherapy test). Overall, this study does add mixed evidence to support salbutamol use in SMA Type 3, though arguably the best piece of evidence comes from the fact that the participants said they objectively felt less fatigued, rather than the modest increase in walking distance. The medication was found to be safe and tolerated well, and the small number of side effects may mean it is reasonable to try salbutamol following discussion with your medical team.     

You can read more about Salbutamol, here.

References

  1. Tiziano FD, Lomastro R, Abiusi E, et al. Longitudinal evaluation of SMN levels as biomarker for spinal muscular atrophy: results of a phase IIb double-blind study of salbutamol, Journal of Medical Genetics Published Online First: 28 December 2018. doi: 10.1136/jmedgenet-2018-105482
     
  2. Kinali M, Mercuri E, Main M, De Biasia F, Karatza A, Higgins R, Banks LM, Manzur AY, Muntoni F. Pilot trial of albuterol in spinal muscular atrophy. Neurology 2002;59:609–10.doi:10.1212/WNL.59.4.609
     
  3. Querin G, D'Ascenzo C, Peterle E, Ermani M, Bello L, Melacini P, Morandi L, Mazzini L, Silani V, Raimondi M, Mandrioli J, Romito S, Angelini C, Pegoraro E, Sorarù G. Pilot trial of clenbuterol in spinal and bulbar muscular atrophy. Neurology. 2013 Jun 4;80(23):2095-8. doi: 10.1212/WNL.0b013e318295d766.
     
  4. Mercuri E, Finkel RS, Muntoni F, Wirth B, Montes J, Main M, et al. SMA Care Group. Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscul Disord 2018;28:103–15.doi:10.1016/j.nmd.2017.11.005