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RNA-based treatments in spinal muscular atrophy

      SMN1 gene is missing in SMA, however only a 5 nucleotid different, homologus, and centromeric gene called SMN2 is maintained. In RNA based therapies the main aim is to be able to obtain more SMN protein transcripts from SMN2. There is a rough inverse correlation between SMN2 copy number and clinical severity. Currently, we have two options. The first one is nusinersen, a molecule that prevents alternative splicing out of exon 7 of the SMN2 gene at the mRNA level so that more transcript is yielded. So, this is an exon inclusion. This molecule has been in practice since the end of 2016, and is recognized globally. So far more than 11,000 patients from all types of SMA has recevied or actively ongoing as a regimen. In SMA I, babies younger than 6 months old are expected to benefit better. The second one is a ‘small modifier molecule’ again hitting the same area in the gene ending with no exclusion of the exon 7, called risdiplam. There are several active studies in different forms of SMA. An initial approval by the FDA has recently become real: SMA I babies older than 2 months based on survival and ventillation prevention facts in the subjects. New and clear data is expected.
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