Treating pediatric neuromuscular disorders: The future is now

Abstract

Pediatric neuromuscular diseases encompass all disorders with onset in childhood and where the primary area of pathology is in the peripheral nervous system. These conditions are largely genetic in etiology, and only those with a genetic underpinning will be presented in this review. This includes disorders of the anterior horn cell (e.g., spinal muscular atrophy), peripheral nerve (e.g., Charcot–Marie–Tooth disease), the neuromuscular junction (e.g., congenital myasthenic syndrome), and the muscle (myopathies and muscular dystrophies). Historically, pediatric neuromuscular disorders have uniformly been considered to be without treatment possibilities and to have dire prognoses. This perception has gradually changed, starting in part with the discovery and widespread application of corticosteroids for Duchenne muscular dystrophy. At present, several exciting therapeutic avenues are under investigation for a range of conditions, offering the potential for significant improvements in patient morbidities and mortality and, in some cases, curative intervention. In this review, we will present the current state of treatment for the most common pediatric neuromuscular conditions, and detail the treatment strategies with the greatest potential for helping with these devastating diseases.

Emery‐Dreifuss muscular dystrophy

“…As in many other hereditary neuromuscular diseases, genetically sophisticated treatments are under investigation for EDMD. A recent study showed that, at least in cell culture, antisense oligonucleotide‐mediated skipping of exon 5 of LMNA can be successfully used, and, therefore, shows promise as a potential therapeutic approach for patients with dominant mutations in this exon . Other molecular strategies that have a possible role in EDMD, such as adeno‐associated virus (AAV)‐based gene replacement and gene‐editing techniques, have not been formally studied in this disease thus far …”

Congenital myopathies: an update

“…The underlying pathomechanisms of congenital myopathies are reviewed elsewhere . Current and future therapeutic approaches to congenital myopathies are elaborated in other reviews . Gene therapy trials are evolving, in particular in X‐linked myotubular myopathy .…”

Recent therapeutic developments of spinal muscular atrophy

“…Nusinersen (Spinraza) was approved as the first drug for the treatment of all types of SMA patients by the United States Food and Drug Administration (FDA) in December 2016, and by the (33). There seems to be a pathophysiologic developmental stage of motor neuron loss in animal models, and once motor neuron loss has progressed beyond a critical point it is unlikely to rescue the disease process (59,60). On the other hand, there is a differential sensitivity due to deficiency in SMN protein, motor neurons being vulnerable.…”