Targeted Treatments for Inherited Neuromuscular Diseases of Childhood

Alex J. Fay, MD, PhD; Renatta Knox, MD, PhD; Erin E. Neil, DO; Jonathan Strober, MD


Semin Neurol. 2020;40(3):335-341. 

In This Article

Abstract and Introduction


In the past decade, the number of genes linked to neuromuscular diseases of childhood has expanded dramatically, and this genetic information is forming the basis for gene-specific and even mutation-specific therapies. At the forefront of these advances are the two recently approved treatments for spinal muscular atrophy: one, an antisense oligonucleotide that modifies splicing of the SMN2 gene, and, the other, a gene therapy vector that delivers the SMN1 gene to motor neurons, both of which are allowing patients to acquire developmental milestones previously unseen in this fatal disease. This review highlights these advances and emerging targeted therapies for Duchenne muscular dystrophy and centronuclear myopathy, while also covering enzyme replacement therapy and small molecule-based targeted therapies for conditions such as Pompe's disease and congenital myasthenic syndromes. With these and other newer techniques for targeted correction of genetic defects, such as CRISPR/Cas9, there is now hope that treatments for many more genetic diseases of the nervous system will follow in the near future.


The list of genes that cause diseases of the peripheral nervous system, which includes the anterior horn cells of the spinal cord, the peripheral nerves, neuromuscular junction, and skeletal muscles, has grown rapidly over the past decade. However, there had been few new therapies, until recently, to match our understanding of the genetic basis of diseases such as spinal muscular atrophy (SMA), Duchenne muscular dystrophy (DMD), and centronuclear myopathy. The last three years have brought two new targeted treatments for SMA and promising preclinical results, and ongoing trials for many other diseases. This review provides an overview of emerging targeted treatments, including gene therapy, antisense oligonucleotides (ASOs), enzyme replacement, and small molecules, for several pediatric neuromuscular disorders, highlighting DMD and SMA and touching on Pompe's disease, congenital myopathies, muscular dystrophies, and myasthenic syndromes (Table 1). We will also provide a basic overview of each type of therapy to give the reader a sense of the generalizability of these approaches to other disorders.