SMN-targeted therapeutics for spinal muscular atrophy: are we SMArt enough yet?
Kathryn J. Swoboda
Kathryn J. Swoboda
Published January 27, 2014
Citation Information: J Clin Invest. 2014;124(2):487-490. https://doi.org/10.1172/JCI74142.
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Commentary

SMN-targeted therapeutics for spinal muscular atrophy: are we SMArt enough yet?

Abstract

Spinal muscular atrophy (SMA) remains one of the most common and lethal autosomal recessive diseases. Homozygous deletion of survival of motor neuron 1 (SMN1) and resulting SMN protein deficiency manifests predominantly with motor neuron degeneration; however, a wealth of emerging data supports a broader influence of SMN deficiency in disease pathogenesis. In this issue of the JCI, Kariya and colleagues demonstrate the relatively selective impact of SMN depletion on the distal motor unit using a series of SMN2-expressing transgenic mice in which constitutive SMN knockdown follows variable periods of normal development. Their observations provide further insights regarding the temporal requirements for SMN in mice, renewing speculation about when and where repletion of SMN is necessary for optimal outcomes in SMA patients.

Authors

Kathryn J. Swoboda

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Figure 1

Denervation status in relation to age in SMA type I and SMA type II.

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Denervation status in relation to age in SMA type I and SMA type II. (A)...
(A) Maximum ulnar CMAP amplitude and (B) MUNE values versus age in SMA type I infants, birth to 24 months. (C) Maximum ulnar CMAP amplitude and (D) MUNE values versus age in SMA type II children from birth to 48 months of age. For all panels, white diamonds indicate presymptomatic infants (identified via genetic testing due to an affected sibling). Black diamonds indicate already symptomatic infants. Adapted with permission from Annals of Neurology (Figures 2 and 3; ref. 20).