Two specific mutations may help in identifying people who are carriers of spinal muscular atrophy (SMA) — those who do not have the disease but can pass it to children — and should be aware before starting a family, a study from Spain reports. The study, “Utility…
Results of an exploratory Phase 2 study evaluating the effectiveness of reldesemtiv (CK-2127107) for a first time in patients with spinal muscular atrophy (SMA) will be presented at the Cure SMA annual conference set for mid-June in Texas. Reldesemtiv is a next-generation fast skeletal muscle troponin activator (FSTA) being developed by Cytokinetics…
Spinraza (nusinersen) improves motor skills in a broad range of children with spinal muscular atrophy (SMA) type 1, including those in more advanced disease stages, according to a study of patients in Germany taking part in an Expanded Access Program (EAP) for the treatment offered by its developer, Biogen. The study,…
A particular type of glial cell — non-neuronal cells of the nervous system — is important in communication between nerve cells and muscles, researchers report. The findings point to potential new targets for therapies that might prevent or lessen muscle fatigue in diseases like spinal muscular atrophy (SMA). The study, “…
Researchers have unraveled the cellular mechanisms behind two RG7916-like splicing modifiers that increase the levels of SMN — the protein missing in spinal muscular atrophy — and suggest these small molecules may indeed lead to treatments of benefit to patients. SMA is caused by mutations in the SMN1 gene, which leads to a reduction in the load of survival motor neuron protein. A second survival motor neuron gene, SMN2, with an identical sequence, can ease the damage done by the mutation but only to a very limited degree. SMN2, like SMN1, is capable of producing SMN. But a slight difference in its DNA sequence leads to an event called alternative splicing (editing) of a premature version of its messenger RNA — the molecule that guides protein production. This difference causes 90 percent of its resulting SMN protein to be shorter and nonfunctional. Several approaches that therapeutically target alternative splicing of SMN2 are currently in various stages of development. These range from an approved antisense oligonucleotide — Spinraza — to small molecules shown to promote the correct splicing of SMN2 mRNA and to increase levels of a functional SMN protein. RG7916 is one of those small molecules, now in three Phase 2 or Phase 2/3 clinical trials for several types of SMA (FIREFISH, SUNFISH, and JEWELFISH). It is an oral treatment intended to bypass the blood-brain barrier and effectively reach the central nervous system, the brain and spinal cord. Latest data from the SUNFISH and JEWELFISH studies showed that RG7916 increases the protein levels of SMN. An additional study in a SMA mouse model found that molecules structurally similar to RG7916 that can modify SMN2 splicing also induce a comparable increase in SMN protein in the animals' blood and brain. Two small molecules structurally similar to RG7916 — called SMN-C2 and SMN-C3 — were found to promote the correct splicing of SMN2, presumably through mechanisms similar to RG7916. Researchers, looking to better understand the mechanisms behind these molecules and potentially help with the design of future splicing modulators, performed a series of chemical and genetic studies. SMN-C2 and SMN-C3 were found to directly bind to SMN2 pre-mRNA, inducing conformational changes that increase the binding of two proteins involved in pre-mRNA splicing, FUBP1 and KHSRP. This binding was shown to increase the correct splicing of SMN2. “These findings underscore the potential of small-molecule drugs to selectively bind RNA and modulate pre-mRNA splicing as an approach to the treatment of human disease,” the researchers wrote.
Long-term treatment with Spinraza (nusinersen) is safe and continues to promote better motor skills and respiratory function in children with spinal muscular atrophy (SMA), according to interim results from a Phase 3 clinical trial. This early data — from the open-label SHINE study — were in the presentation “Longer-term…
Spinraza (nusinersen) improves motor and respiratory function in children with spinal muscular atrophy (SMA), according to results from different trials. Biogen will present the data at the American Academy of Neurology annual meeting, taking place April 21-27 in Los Angeles. SMA is a neurodegenerative disease caused by mutations in the SMN1 gene, which provides…
A new genetic approach to restore the expression of the gene that causes spinal muscular atrophy (SMA) in patients’ cells holds promise to effectively and permanently treat the disease, researchers suggest. The study, “Seamless genetic conversion of SMN2 to SMN1 via CRISPR/Cpf1 and single-stranded oligodeoxynucleotides in…
Approval of Spinraza (nusinersen), the first disease-modifying therapy for spinal muscular atrophy (SMA), has brought not only hope, but also some challenges for both patients and researchers, according to a recent review. The study, “Advances in therapy for spinal muscular atrophy: promises and challenges,” was published…
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