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Spinal muscular atrophy (SMA) is a rare autosomal recessive neuromuscular disorder characterised by loss of motor neurons in the spinal cord and proximal muscle weakness. It is caused by deletions or mutations in the survival motor neuron 1 (SMN1) gene, which leads to deficiency of the SMN protein critical for motor neuron function. Based on age of onset and maximum motor function, SMA is classified into types 0-4.

SMA effects approximately 1 in 10,000 births, infant mortality varies greatly on the severity of SMA. It is estimated that there are 25,000 Americans currently living with SMA, and speculated there’s somewhere between 500 and 2,000 in the UK.

Patients with SMA can experience a range of symptoms depending on the severity of the disorder (defined by types 0-4), these range from weak arms and legs, movement problems, muscle tremors, bone/ joint problems, to breathing difficulties.

There are 90 active clinical trials for SMA listed on (a drop in the ocean against the 65,000 active studies listed). Due to the nature of this disorder a majority are conducted in paediatric patient groups.

Clinical Trial Challenges

  • Small patient pool - The rarity of SMA, combined with low infant mortality rates makes trial participant recruitment difficult.

  • Narrow treatment window – Many therapies and interventions may only be effective if administered very early.

  • Heterogeneous populations - The wide range of disease severity makes defining homogeneous treatment groups problematic.

  • Validated clinical endpoints - Identifying outcome measures sensitive to treatment response has been an obstacle.

  • Sham surgery controls - Gene therapy trials must determine appropriate control groups.

Despite these hurdles, SMA clinical research has achieved significant advancements in recent years

  • Biogen: The first FDA-approved SMA treatment, nusinersen, was based on successful Phase 1-3 trials showing improved motor function across SMA types.

  • Novartis: The gene therapy Zolgensma demonstrated dramatic efficacy in improving survival and milestones in young Type 1 SMA patients.

  • Genentech: Risdiplam has been approved by the FDA as an oral alternative to intrathecal injection treatments.

Further Reading & References:


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