Spinal Muscular Atrophy (SMA) is a progressive neurodegenerative disorder characterised by the loss of upper and/or lower motor neurons. SMA is the leading genetic cause of infant mortality with an incidence of 1 in 6000 live births and a carrier frequency of about 1 in 50. Different types of disease (from SMAI to SMAV) have been described based on clinical severity and age of onset. The SMA-determining gene, Survival of Motor Neurons (SMN), is part of a 500 kb-inverted duplication on chromosome 5q13. Within the duplicated genes SMN1 and SMN2 can be found. Most (95%) SMA patients have deletions or conversion events of SMN1. The SMN2 gene primarily produces a transcript which lacks exon 7 and of which only 10-20% of its protein is functional. Although a variety of therapeutic trials are ongoing, only life-prolonging treatments are being developed. The knowledge gained regarding the pathogenesis of SMA remains limited, because the precise function of SMN is not yet known. Furthermore, it is not quite clear why motor neurons of the patients are the only cell type for which SMN expression level are unadequate for their normal activity, even if the affected genes have “housekeeping” functions. Both pharmacological or genetic approaches have been conducted for the therapy of SMA. Moreover, stem cells provide a further aspect to be analysed. In fact, the genetic modification of a small number of stem cells could give rise to a dividing population of therapeutic cells. These innovative approaches when united could be usefully adopted to replace lost cells and at the same time protect surviving motor neurons in SMA patients.
Keywords: Spinal Muscular Atrophy, gene therapy, gene targeting, pharmacological treatment, survival motor neuron gene
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