Spinal muscular atrophy (SMA) is a rare neuromuscular disorder characterized
by the degeneration of motor neurons (MNs) in the spinal cord resulting in
progressive muscle atrophy and weakness. Due to its early onset and severity of symptoms, SMA is notable in the health care community as one of the most common
causes of early infant death. SMA is caused by missing a functional survival motor
neuron 1 (SMN1) gene in patients who produce deficient levels of survival motor
neuron (SMN) protein from a copy gene (SMN2), but that could not sustain the survival
of spinal cord MNs. Before the end of 2016, there was no cure for SMA, and
management only consisted of supportive care. Since then, several therapeutic
strategies to increase SMN protein have developed and are currently in various stages
of clinical trials. The SMN2-directed antisense oligonucleotide (ASO) therapy was first
approved by the FDA in December 2017. Subsequently, in May 2019, gene therapy
using an adeno-associated viral vector to deliver the DNA sequence of SMN protein
was also approved. These two novel therapeutics have a common objective: to increase
the production of SMN protein in MNs, and thereby improve motor function and
survival. Treating patients with SMA brings new responsibilities and unique dilemmas.
As SMA is such a devastating disease, it is reasonable to assume that a single
therapeutic modality may not be sufficient. Neither therapy currently available provides
a complete cure. Several other treatment strategies are currently under investigation.
These include: establishing an early diagnosis to enable early treatment, a combination
of the different treatment regimens, and frequency, dosage, and route variations of drug
delivery. Understanding the underlying mechanisms of these treatments is the other
area of needed study.
Keywords: Clinical trial, Novel therapy, Spinal muscular atrophy, Survival motor
neuron protein.
