SMA seems to appear de novo (i.e., without any hereditary causes) in around 2–4% of cases.Spinal muscular atrophy affects individuals of all ethnic groups, unlike other well known autosomal recessive disorders, such as sickle cell disease and cystic fibrosis, which have significant differences in occurrence rate among ethnic groups. The overall prevalence of SMA, of all types and across all ethnic groups, is in the range of 1 per 10,000 individuals; the gene frequency is around 1:100, therefore, approximately one in 50 persons are carriers. There are no known health consequences of being a carrier. A person may learn carrier status only if ones child is affected by SMA or by having the SMN1 gene sequenced.Affected siblings usually have a very similar form of SMA. However, occurrences of different SMA types among siblings do exist – while rare, these cases might be due to additional de novo deletions of the SMN gene, not involving the NAIP gene, or the differences in SMN2 copy numbers. Diagnosis
SMA is diagnosed using genetic testing that detects homozygous deletion of the SMN1 gene in over 95% of cases, and a compound SMN1 mutation in the remaining patients.
It is currently not used due to the risk of severe side effects related to long-term use. A 2019 meta-analysis suggested that VPA may offer benefits, even without improving functional score. Hydroxycarbamide (hydroxyurea) was shown effective in mouse models and subsequently commercially researched by Novo Nordisk, Denmark, but demonstrated no effect on people with SMA in subsequent clinical trials.Compounds which increased SMN2 activity in vitro but did not make it to the clinical stage include growth hormone, various histone deacetylase inhibitors, benzamide M344, hydroxamic acids (CBHA, SBHA, entinostat, panobinostat, trichostatin A, vorinostat), prolactin as well as natural polyphenol compounds like resveratrol and curcumin. Celecoxib, a p38 pathway activator, is sometimes used off-label by people with SMA based on a single animal study but such use is not backed by clinical-stage research. SMN stabilisation
SMN stabilisation aims at stabilising the SMNΔ7 protein, the short-lived defective protein coded by the SMN2 gene, so that it is able to sustain neuronal cells.No compounds have been taken forward to the clinical stage. Aminoglycosides showed capability to increase SMN protein availability in two studies. Indoprofen offered some promise in vitro. Neuroprotection
Neuroprotective drugs aim at enabling the survival of motor neurons even with low levels of SMN protein. Olesoxime was a proprietary neuroprotective compound developed by the French company Trophos, later acquired by Hoffmann-La Roche, which showed stabilising effect in a phase-II clinical trial involving people with SMA types 2 and 3.