Abstract
Spinal muscular atrophy (SMA) is a progressive pediatric neuromuscular disease. Because disease severity is related to survival motor neuron (SMN) protein levels, increasing SMN production from the SMN2 gene has been a major SMA drug-discovery strategy. Cell-based assays using neuronal cell lines and cells from SMA patients have identified compounds that can increase SMN protein expression. Our experience of using such an assay signaled potential risks to be avoided through the use of appropriate secondary assays. In addition to the ‘SMN2’ approach, compensating for decreased SMN protein or neuroprotection are also potential SMA drug-discovery strategies. SMA clinical trials are now a reality; however, trial design in a slowly progressing rare disease such as SMA will present an interesting future challenge.
Acknowledgements
We are grateful to colleagues at Trophos who helped the realization of the SMA drug-discovery program and especially Delphine Maux, Pascale Galéa and the HTS team for having performed the ‘SMN2’ screening campaign.
Financial & competing interests disclosure
Invaluable financial support and encouragement was provided by the Association Française contre les Myopathies. Authors are employees of Trophos SA (France). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.