Spinal muscular atrophy: From animal model to potential treatments

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of the anterior horn cells of the spinal cord leading to muscular paralysis and atrophy. SMA is the second commonest genetic cause of death in childhood affecting approximately 1 in 10,000 live births, but no effective treatment is currently available. Due to gene deletions, mutations, or conversions, the telomeric copy of the survival of motor neuron (SMN) gene is abnormal in more than 96% of patients with clinically typical SMA. The identification of SMN-interacting protein strongly suggests that it is involved in the assembly of the spliceosome, processing of pre-mRNA splicing, transcription, and metabolism of ribosomal RNA. Mouse models of human SMA have been established through a combination of knockout and transgenic techniques. These SMA-like mice genotypically and phenotypically mimic SMA patients. They should be useful in elucidating the physiological functions of SMN protein, understanding the pathophysiology of the disease, and also providing a biological system for use in drug testing or stem cell and gene therapies. Recent advances concerning SMN functions and the potentialities of different SMA therapies are discussed.