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MOTOR NEURON DISEASE

Maybe too much of a good thing in gene therapy

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Gene replacement therapies have shown remarkable advances recently, including onasemnogene abeparvovec for treatment of symptomatic and presymptomatic patients with spinal muscular atrophy. A recent report by Van Alstyne and colleagues in a mouse model of spinal muscular atrophy raises concerns that such treatment can generate toxic overexpression of SMN protein.

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Fig. 1: Comparison of three drugs approved for treatment of patients with spinal muscular atrophy, and potential implications of overexpression of SMN protein in neurons.

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Authors and Affiliations

  1. Center for Experimental Neurotherapeutics, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA

    Richard S. Finkel

  2. Neurogenetics Branch, NINDS, NIH, Bethesda, Maryland, USA

    Kenneth H. Fischbeck

Authors
  1. Richard S. Finkel
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  2. Kenneth H. Fischbeck
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Corresponding authors

Correspondence to Richard S. Finkel or Kenneth H. Fischbeck.

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Competing interests

R.S.F. is an advisor to and investigator in clinical trials sponsored by AveXis/Novartis Gene Therapies, Biogen, and Roche; and has been an advisor to Scholar Rock, Cure SMA, SMA Europe, and the n-Lorem Foundation. K.H.F. has been an unpaid consultant and collaborator with Ionis, Biogen, Novartis, and the SMA Foundation.

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Finkel, R.S., Fischbeck, K.H. Maybe too much of a good thing in gene therapy. Nat Neurosci 24, 901–902 (2021). https://doi.org/10.1038/s41593-021-00882-w

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