News

Two years after approving it, the 28-member European Union will begin enforcing its General Data Protection Regulation (GDPR) — a tough new law that aims to protect the EU’s 512 million citizens, including rare disease patients, from having their medical records misused, sold, or subject to extortion by hackers, third parties…

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…

If 8-year-old Branden Lim had been born in Australia instead of Malaysia, his parents soon would have no problem obtaining Spinraza (nusinersen) to treat his spinal muscular atrophy (SMA). Australian Health Minister Greg Hunt recently announced that, effective June 1, his ministry would add the Biogen therapy to its Pharmaceutical…

The National Organization for Rare Disorders (NORD) will celebrate the 35th anniversary of both the 1983 Orphan Drug Act and NORD’s founding at a dinner tonight in Washington, D.C. The 2018 Rare Impact Awards, to be held at the Andrew W. Mellon Auditorium, will be webcast via Facebook for those…

Patients with spinal muscular atrophy (SMA) types 2 and 3 are at risk of malnutrition, altered metabolic rates, and changes in body composition, a study reports. The study, “Comprehensive nutritional and metabolic assessment in patients with spinal muscular atrophy: Opportunity for an individualized approach,” appeared in…

The European Union isn’t doing enough to protect the 30 million or so people with rare diseases who live in its 28 member countries, officials meeting last week in Vienna said. More than 900 people from 58 nations attended the 9th European Conference on Rare Diseases & Orphan Drugs (ECRD), held…

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, “…

Over the next 20 years, the number of Americans with spinal muscular atrophy (SMA) will rise from 10,000 to nearly 15,000 — and 8,000 of those living with SMA today will still be alive come 2038, predicts Kenneth Hobby, president of Cure SMA. The Chicago-based nonprofit has been working…

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.