SMA: from gene discovery to gene therapy

Médecine sciences : M/S
Martine Barkats

Abstract

Spinal muscular atrophy (SMA) is the most common genetic disease leading to infant mortality. This neuro-muscular disorder is caused by the loss or mutation of the telomeric copy of the 'survival of motor neuron' (Smn) gene, termed SMN1. Loss of SMN1 leads to reduced SMN protein levels, inducing degeneration of motor neurons (MN) and progressive muscle weakness and atrophy. Gene therapy, consisting of reintroducing SMN1 in the MNs, is an attractive approach for SMA. We showed the most efficient rescue of SMA mice to date after a single intravenous injection of an AAV9 expressing SMN1, highlighting the considerable potential of this method for the treatment of human SMA. Recently, a startup led by the Dr Kaspar decided to test this experimental approach in children with SMA type 1. Dr Mendell, in charge of this clinical project, showed a very significant increase of the lifespan and motor function of the patients (until 4 years) after a single injection of AAV9-SMN1 (named ZolgenSMA®) into an arm or leg vein. This gene therapy treatment obtained a marketing authorization by the FDA in May 24 and is now the first efficient therapy for neuromuscular disease.

References

Feb 1, 1970·Archives of Disease in Childhood·D F RobertsS D Court
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Aug 7, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Douglas M McCarty
Dec 23, 2008·Nature Biotechnology·Kevin D FoustBrian K Kaspar
Apr 16, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Sandra DuqueMartine Barkats
Dec 2, 2010·Human Molecular Genetics·Elisa DominguezMartine Barkats
Apr 13, 2011·Archives of Neurology·Stephen J Kolb, John T Kissel
Apr 14, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Steven J GrayR Jude Samulski
Aug 4, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Adam K BevanBrian K Kaspar
Jul 6, 2017·Orphanet Journal of Rare Diseases·Ingrid E C VerhaartHanns Lochmüller

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Citations

May 2, 2020·Médecine sciences : M/S·Alain FischerMichel Goldman

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