For our lower motor neurons to function and remain healthy, our cells need to produce the survival motor neuron (SMN) protein. The ability to do this is mainly controlled by the survival motor neuron 1 (SMN1) gene.
The SMN2 gene also contributes to the production of SMN protein, though it only makes approximately 10% of that produced by SMN1. For this reason, SMA is caused only by mutations in the SMN1 geneand not SMN2, and also why SMN2 is often called the SMN ‘back-up’gene.
Anyone who has SMA has at least one copy of the SMN2 gene. Individuals can have multiple copies of SMN2, and, in general, it seems that those with more copies have a less severe form of SMA.
Most of the SMN protein made by SMN2 (about 90%) is missing an important piece called exon 7. The remaining 10% of the protein produced by SMN2 includes exon 7 and is the same as that made bySMN1. A number of treatment strategies that target SMN2 to make more functional SMN protein are being explored; they aim to do this in one of three main ways:
Antisense oligonucleotide drugs are small snippets of synthetic genetic material that bind ribonucleic acid (RNA). They are often described as molecular patches because they can be specifically designed to target and affect how a particular gene is read. ASOs have great potential for SMA, because they can accurately target the SMN2 gene to essentially convert it into the SMN1 gene, i.e. they are small molecules “patching-up” SMN2 to act more like SMN1. They do this by binding to the RNA template made by SMN2 and enhancing the inclusion of exon 7 into the SMN protein.
Biogen – nusinersen (Spinraza™): the registry of clinical trials.
In April 2020, Biogen initiated a new study called DEVOTE, a clinical trial that evaluates the safety and efficacy of higher doses of nusinersen (brand name Spinraza®). The goal of the study is to find out whether higher doses of nusinersen may provide additional benefit to people being treated for SMA.
Find out more through this brochure, developed by Biogen.