Motor Neuron Biology and Disease: A Current Perspective on Infantile-Onset Spinal Muscular Atrophy

Abstract

Infantile-onset spinal muscular atrophy (SMA) serves as an excellent paradigm in which to investigate selective neurodegenerative phenotypes. Caused by low levels of the ubiquitously expressed survival motor neuron (SMN) protein, the disease mainly targets the spinal motor neurons. This selective phenotype remains largely unexplained, but has not hindered the development of SMN repletion as a means to a treatment. Here, we chronicle recent advances in the area of SMA biology. We provide a brief background to the disease, highlight major advances that have shaped our current understanding of SMA, trace efforts to treat the condition, discuss the outcome of two promising new therapies and conclude by considering contemporary as well as new challenges stemming from recent successes within the field.

Keywords::

• motor neuron
• neurodegeneration
• spinal muscular atrophy
• survival motor neuron
• therapies

Financial & competing interests disclosure

Work in the authors’ laboratory is supported by AFM-France, Cure SMA and grants from the National Institutes of Health (R01 NS057482, R21 NS0999921 and R56 NS104218). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Acknowledgements

We apologize to those of our colleagues whose original work could not be cited in this article owing to space restrictions.

Additional information

Funding

Work in the authors’ laboratory is supported by AFM-France, Cure SMA and grants from the National Institutes of Health (R01 NS057482, R21 NS0999921 and R56 NS104218). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.