Abstract
Spinal muscular atrophy (SMA) is one of the most common autosomal recessive diseases with progressive weakness of skeletal and respiratory muscles, leading to significant disability. The disorder is caused by mutations in the survival motor neuron 1 (SMN1) gene and a consequent decrease in the SMN protein leading to lower motor neuron degeneration. Recently, Food and Drug Administration (FDA) and European Medical Agency (EMA) approved the antisense oligonucleotide nusinersen, the first SMA disease-modifying treatment and gene replacement therapy by onasemnogene abeparvovec. Encouraging results from phase II and III clinical trials have raised hope that other therapeutic options will enter soon in clinical practice. However, the availability of effective approaches has raised up ethical, medical and financial issues that are routinely faced by the SMA community. This review covers the available data and the new challenges of SMA therapeutic strategies.
Highlights
Spinal muscular atrophy (SMA) is a heterogeneous hereditary neuromuscular disease, presenting with progressive weakness of skeletal and respiratory muscles, leading to muscle atrophy and significant disability
The disease is caused by a homozygous deletion or a heterozygous deletion combined with point mutation on the other allele on the survival motor neuron 1 (SMN1) gene on chromosome 5q and consequential lack of the Survival Motor Neuron (SMN) proteins, causing degeneration of lower motor neurons [1,2]
One study reported the results of a number needed to treat (NNT) analysis comparing the efficacy of nusinersen and onasemnogene abeparvovec on several outcomes using data from AVXS-101-CL-101 and ENDEAR studies in symptomatic SMA type I
Summary
Spinal muscular atrophy (SMA) is a heterogeneous hereditary neuromuscular disease, presenting with progressive weakness of skeletal and respiratory muscles, leading to muscle atrophy and significant disability. I and II patients often present failure to thrive and dysphagia and require to increase nutritional uptake with the use of hyperproteic and hypercaloric oral supplements or, in the more severe cases, gastrostomy placement. These patients require a multidisciplinary rehabilitative approach covering respiratory, orthopedic, psychological, physio- and speech-therapist and nutritional care [4,5]. SMN1 gene (onasemnogene abeparvovec) and in treatments targeting SMN—Independent Factors enhancing therapiestherapies and neuroprotection). Figure their mechanisms mechanisms of of action. This review covers the available data of SMA therapeutic strategies in pre-clinical development, currently tested in clinical trials and available in clinical practice
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