Disease-Modifying Therapy Treatments for 5-q Spinal Muscular Atrophy

Abstract

Spinal muscular atrophy (SMA) is the second most prevalent autosomal recessive disorder affecting children and generating disability and reduced quality of life. It can lead to death in a severe form. The most common form of SMA is 5q SMA, which accounts for more than 95% of all cases, resulting from mutations in the survival of motor neuron 1 (SMN1) leads to a shortage of SMN protein which results in a loss of motor neurons in the spinal cord. The severity of the manifestation of SMA strongly correlates with SMN protein expression. Therefore, restoration of SMN1 and upregulation of SMN2 are targeted for promising effective therapies. In the last two years, the number of studies and trials of evaluating the efficacy and safety of the disease-modifying therapies for treating SMA patients has rapidly expanded. Hence, the aim of this systematic review was conducted to evaluate and analyze the effect of disease-modifying treatments on motor function, survival or permanent ventilation, and any side effects on patients with SMA type I, II, and III age from birth to 65 years old, with confirmed their diagnosis with 5-q SMA, and compared the results with placebo, or natural history controls. I searched five electronic databases, and the articles fulfilling the criteria were selected and the data extracted and reported. Ten references included: seven references met the criteria for this review and three did not, and due to few studies that found, and none of the gene therapy and branaplam trials met the criteria, I decided to include them. The main findings demonstrated that, despite the heterogeneity and wide variation in the reported outcomes, there is excellent safety and efficacy in these approved therapies. However, there are some limitations in sample size and long-term data for these patients. So, these discoveries raised the requirement of newborn screening for SMA and applied the standardized outcome measures to obtain the maximal efficacy of the available treatment options and to be able to compare between results and to balance the data from different registries. Also, require well-designed studies and combinations of therapy evaluation concerning ethical and financial issues.