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Spinal Muscular Atrophy

What is Spinal Muscular Atrophy?

Spinal Muscular Atrophy (SMA) is a rare genetic disorder that affects motor neurons responsible for movement. It is caused by a deficiency in the survival motor neuron 1 (SMN1) gene, which results in decreased production of the SMN protein that is essential for motor neuron survival, thereby affecting the patient's movement, respiration, swallowing, as well as multiple organs such as the spleen, heart, pancreas, and even threatening the patient's life. SMA affects approximately 1 in 10,000 live births and is the leading genetic cause of infant mortality.

Cure Spinal Muscular Atrophy's Approach

SMN Dependent Therapeutic Strategies

  • Gene therapy
  • SMN2 promoter activation
  • SMN2 splicing modulation

SMN Independent Therapeutic Strategies

  • Muscle enhancement: Prevents and restores motor function loss
  • Neuroprotection: Protects against neuronal injury or degradation
  • Neuronal function: Enhances neuronal transmission

There are currently three SMA therapeutics: the antisense oligonucleotide (ASO) drug Spinraza, the small molecule drug Risdiplam, and the AAV gene therapy Zolgensma. Among them, Spinraza and Risdiplam have limited efficacy and a short duration of action, requiring patients to repeatedly use these expensive drugs.

Fig. 1 Therapeutic approaches for SMA.Fig. 1 Therapeutic approaches for SMA. (Chen T H, 2020)

Gene Therapy for Spinal Muscular Atrophy

Over the past few decades, significant advances have been made in the field of gene therapy, which involves the introduction of a healthy copy of the SMN1 gene into the patient's cells. Gene therapy for SMA has shown promising results in clinical trials and led to gene therapy drug approval by the US FDA.

Zolgensma is a revolutionary and highly innovative one-time gene therapy designed to address the genetic root cause of SMA disease by replacing the function of the missing or non-functioning SMN1 gene. Following a single intravenous infusion administration, Zolgensma introduces a functional copy of the SMN1 gene into the patient's cells and continuously expresses functional SMN proteins to halt the disease process, thereby improving patient survival over time. Clinical studies have shown that in patients with symptomatic and presymptomatic SMA, Zolgensma gene therapy demonstrated significant clinically meaningful therapeutic benefits, including prolonged event-free survival and achievement of motor milestones not seen in the natural history of the disease. The FDA has approved Zolgensma for children under the age of 2 years.

Current Gene Therapy Clinical Trials in Spinal Muscular Atrophy

There are currently several ongoing clinical trials investigating the safety and efficacy of gene therapy for SMA. One such trial is the gene transfer clinical trial for SMA Type 1, which is testing the safety and efficacy of intravenous delivery of AVXS-101 as a treatment for SMA Type 1. Another ongoing clinical trial is the evaluation of the efficacy, safety, and tolerability of intrathecal (IT) OAV101 in pediatric patients aged ≥2 to <18 years with SMA type 2. In addition to these trials, there are also several current clinical trials investigating the safety and efficacy of non-viral gene therapies for SMA.

Although SMA genetics are complex, the fact that the disease is monogenic and low levels of functional SMN exist creates an ideal environment for vector-mediated gene replacement. Ongoing trials are pioneering first-in-human experiments. The basic and translational research underpinning the current SMA gene therapy trials provides a solid foundation of hope for SMA patients and patients with many other rare diseases who can benefit from highly targeted vector-mediated gene replacement strategies.


  • Chen, T. H. New and developing therapies in spinal muscular atrophy: from genotype to phenotype to treatment and where do we stand? International journal of molecular sciences, 2020, 21(9): 3297.

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