organ specific redox imbalances in spinal muscular atrophy mice are partially rescued by smn antisense oligonucleotides

Original title: “Organ-specific redox imbalances in spinal muscular atrophy mice are partially rescued by SMN antisense oligonucleotides.”

A similar expansion is underway with AAV9 vectors, which can cross the blood–brain barrier via intravascular delivery to treat inherited diseases of the CNS, as first demonstrated with Zolgensma for SMA. 196 , 197 , 198 , 199 , 200 For those interested in tracking marketed gene (and cell) therapies across the world, the International Society for Stem Cell Research maintains an up‐to‐date map.

Original title: “Clinical applications of gene therapy for rare diseases: A review - PMC”

The FDA has approved Novartis’ intrathecal formulation of onasemnogene abeparvovec-brve, marketed as Itvisma, for patients ages 2 years and older living with spinal muscular atrophy. "Itvisma is the first IT AAV9 gene therapy approved, but treatments for many other diseases using AAV9, or variants of AAV9, will soon follow. Itvisma’s approval opens the door for an exciting era of definitive treatments for neurological disorders with genetic features." STEER, a 52-week study, comprised 126 treatment-naïve patients with SMA Type 2 who were randomly assigned 1:1 to either Itvisma or sham procedure, followed by a crossover phase. In the trial, those on the intrathecal medication demonstrated a statistically significant 2.39-point improvement on HFMSE vs 0.51 points for those on sham (P = .0074). STEER, the most notable of the trials, met its primary end point, as treatment with the intrathecal formulation led to significant enhancements in motor function, assessed through total Hammersmith Functional Motor Scale-Expanded (HFMSE) scores. "Itvisma is the first systemic gene therapy available to a large population of adults, so many providers and institutions that care for adults will have their first experience with this revolutionary treatment modality. This trial included 23 sitting, nonambulatory patients with SMA testing three dose levels across two age groups (6 to <24 months and 24 to <60 months). After 12 months, older patients in the medium-dose cohort (1.2 x 10¹⁴ vg) showed significant improvements in HFMSE scores compared with historical controls, reaching roughly twice the accepted minimal clinically meaningful difference (P <.01).3 STRENGTH differed slightly from STEER in that it tested safety, tolerability, and efficacy of the intrathecal medication in patients with SMA who discontinued previously approved treatments nusinersen (Spinraza; Biogen) or risdiplam (Evrysdi; Genentech). The open-label, single-arm study included 27 patients with a mean age of 7.4 years and were on risdiplam or nusinersen for a mean duration of 2.98 and 4.32 years, respectively. ... Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, Itvisma continued to maintain a similar safety profile that was observed in STEER.

Original title: “FDA Approves New Intrathecal Administration Route for Spinal Muscular Atrophy Gene Therapy | NeurologyLive - Clinical Neurology News and Neurology Expert Insights”

The U.S. Food and Drug Administration today approved Itvisma (onasemnogene abeparvovec-brve) for the treatment of spinal muscular atrophy (SMA) in adult and pediatric patients 2 years of age and older with confirmed mutation in the survival motor neuron 1 (SMN1) gene.

Original title: “FDA Approves Gene Therapy for Treatment of Spinal Muscular Atrophy”