Spinraza (nusinersen) / Biogen, Ionis, Royalty - LARVOL DELTA

Real-World Treatment Patterns in Patients with Spinal Muscular Atrophy Receiving Multiple Disease-Modifying Therapies. (PubMed, Adv Ther) - "Following widespread NBS, OAV had the highest utilization among patients age ≤ 2 years as first or second DMT after nusinersen or risdiplam. Use of a second DMT type was lowest among patients who initiated OAV."

HEOR • Journal • Real-world evidence • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Serum circulating cell-free messenger RNA profile response to risdiplam treatment in adult patients with late-onset spinal muscular atrophy. (PubMed, Brain Commun) - "A separate exploratory subgroup of patients switching from nusinersen to risdiplam (n = 7) was analysed at comparable time points. Serum ccfmRNA profiles distinguish adult loSMA from controls and capture risdiplam-associated molecular responses. These findings support the concept that serum ccfmRNA profiling may provide a useful exploratory framework for studying disease-associated and treatment-associated molecular changes in adult loSMA."

Journal • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

An OLIP Study (Open Label Individual Patient) of Nusinersen in a Participant With Spinal Muscular Atrophy Who Previously Participated in an Investigational Study With Nusinersen (clinicaltrials.gov) - P=N/A | N=1 | Not yet recruiting | Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

New trial • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Spinal muscular atrophy as a blueprint for precision therapy in neuromuscular disease. (PubMed, Expert Rev Mol Med) - "The evolution of SMA therapies has transformed neurogenetics. Clinical benchmarks have successfully shifted from reactive, symptomatic management to proactive, molecularly targeted precision medicine."

Journal • Review • CNS Disorders • Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMA4 • SMN1 • SMN2

Spinal Muscular Atrophy, Sleep-Disordered Breathing, and the Effects of Disease-Modifying Therapies: A Narrative Review. (PubMed, Pediatr Neurol) - "Much of existing medical literature regarding SDB in SMA and the impact of DMTs is derived from studies of small sample sizes, abstracts, and varying methodologic rigor. To advance our understanding of DMTs' effects on the management and potential prevention of SDB in SMA, rigorous, multicenter, blinded prospective cohort studies with large sample sizes are essential. Furthermore, specific attention should be directed toward assessing the superiority of single-agent therapy versus combination therapy in mitigating the morbidity associated with SDB in SMA."

Journal • Review • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Novel Coronavirus Disease • Obstructive Sleep Apnea • Rare Diseases • Respiratory Diseases • Sleep Apnea • Sleep Disorder

A changing early onset scoliosis phenotype in spinal muscular atrophy: nusinersen treatment is associated with younger age, increased curve magnitude, and kyphosis at the time of index surgery. (PubMed, Spine Deform) - "Nusinersen exposure was associated with younger age at surgery, greater curve magnitude, and increased kyphosis. These findings highlight potential changes in the phenotype of surgical candidates with EOS and SMA among patients treated with Nusinersen."

Journal • Genetic Disorders • Movement Disorders • Muscular Atrophy • Pediatrics • Rare Diseases

Depression among caregivers of children with spinal muscular atrophy type 1: a single-centre paediatric pulmonology experience (ERS 2026) - "All patiens were receiving nusinersen therapy, and 75.6% had additionally received gene therapy...No association was observed between caregiver depression scores and tracheostomy status (p=0,83). These findings support the integration of routine psychological screening and psychosocial support into multidisciplinary care for children with SMA."

Clinical • CNS Disorders • Depression • Gene Therapies • Genetic Disorders • Mood Disorders • Movement Disorders • Muscular Atrophy • Pediatrics • Psychiatry • Rare Diseases • Respiratory Diseases

Respiratory Trajectories in Children with Type I and II Spinal Muscular Atrophy in the Era of Disease modifying Therapies (ERS 2026) - "First line treatment was Nusinersen for 22 (73%), Risdiplam for 3 (10%) and Onasemnogene Aberparvovec for 5 (17%) patients... Respiratory function in children with type I and II SMA treated by DMTs remains severely impaired, with a need for intensive care, airway clearance devices and early initiation of NIV. Early respiratory interventions may stabilize respiratory function and improve outcomes."

Clinical • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Clinical analysis of nusinersen for spinal muscular atrophy types 2 and 3 in children (PubMed, Zhongguo Dang Dai Er Ke Za Zhi) - "Nusinersen is well tolerated and safe in children with SMA types 2 and 3. The proportions achieving clinically meaningful responses on motor-function scales and CMAP improvements increase over time, and rehabilitation training may enhance efficacy."

Journal • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Consensus on gene therapy for spinal muscular atrophy in Taiwan. (PubMed, J Formos Med Assoc) - "The advent of three FDA-approved disease-modifying therapies-onasemnogene abeparvovec, nusinersen, and risdiplam-has markedly improved therapeutic prospects...This consensus recommends incorporating SMA into the newborn screening program for early diagnosis and prompt treatment, and emphasizes that gene therapy should be evaluated based on SMN2 copy number and clinical condition. Presymptomatic treatment is critical for optimal motor outcomes, and multidisciplinary care teams are essential for comprehensive long-term management."

Journal • Review • CNS Disorders • Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Pediatrics • Rare Diseases • SMA4 • SMN1 • SMN2

Noninfectious meningitis related to nusinersen: a pharmacovigilance analysis using the WHO database. (PubMed, Neuromuscul Disord) - "Awareness of non-infectious meningitis as a potential adverse reaction associated with nusinersen can simplify diagnosis and contribute to timely treatment. The benefits of nusinersen in terms of improving motor function and survival in patients with SMA clearly outweigh the rare risks."

Adverse events • Journal • CNS Disorders • Genetic Disorders • Infectious Disease • Movement Disorders • Muscular Atrophy • Rare Diseases

UK SMA patient registry: a 3-year patient-reported outcome measures study supporting the drug appraisal of Nusinersen and Risdiplam in spinal muscular atrophy. (PubMed, J Neurol Sci) - "The study demonstrated the successes of implementing PROMs to support MAA data collection and marked an important milestone for patients' voices to contribute to SMA therapy evaluation through a patient registry. The study data emphasises that patient-reported data complements and offers an alternate perspective to clinical real-world data."

Journal • CNS Disorders • Depression • Genetic Disorders • Mood Disorders • Movement Disorders • Muscular Atrophy • Psychiatry • Rare Diseases

Spinal muscular atrophy in the disease-modifying therapy era: successes, limitations and future directions. (PubMed, Front Mol Med) - "In recent years, three FDA-approved disease-modifying therapies, nusinersen, risdiplam, and onasemnogene abeparvovec, have improved the quality of life for patients with SMA and have eased the management of associated symptoms. However, unmet needs remain as comorbidities become increasingly apparent in the era of disease-modifying therapies. Despite the remarkable progress achieved over the past decade, continued research is essential to further improve the quality of life, clinical outcomes, and standard of care for individuals living with SMA."

Journal • Review • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • Respiratory Diseases

Respiration during sleep in children with spinal muscular atrophy type 2 and 3, treated with nusinersen or risdiplam. (PubMed, Sleep Med) - "Over the study period, DMTs were associated with stabilization or improvement of sleep-related respiration in both SMA type 2 and 3. This included reduced SDB in type 2 and improved TAA in type 3, with no evidence of respiratory decline."

Journal • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • Sleep Disorder

Case Report: Ultra-early nusinersen initiation with pre-procedural spinal ultrasound-assisted intrathecal access in a symptomatic neonate with spinal muscular atrophy. (PubMed, Front Pediatr) - "This case provides an individual-level real-world description of symptomatic neonatal spinal muscular atrophy treated within the first days of life after postnatal diagnosis. It also supports the feasibility of a structured ultrasound-assisted approach for early repeated intrathecal administration during the neonatal period."

Journal • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMA4 • SMN1 • SMN2

A Study to Find Out How Nusinersen is Processed in the Body When Given Through the ThecaFlex DRx System in Adult and Pediatric Participants With Spinal Muscular Atrophy (PIERRE-PK) (clinicaltrials.gov) - P1 | N=78 | Recruiting | Sponsor: Biogen | N=58 ➔ 78 | Trial completion date: Jun 2027 ➔ Sep 2027 | Trial primary completion date: Jun 2027 ➔ Sep 2027

Enrollment change • Trial completion date • Trial primary completion date • Muscular Atrophy

Real-world pharmacoclinical implementation of risdiplam under a national SMA protocol: A hospital pharmacy registry-based case series. (PubMed, Pak J Pharm Sci) - "Risdiplam was used appropriately in accordance with protocol criteria. Registry incompleteness, rather than clinical deviation, was the main limitation and standardized data capture is essential for real-world evaluation."

Journal • Real-world evidence • Retrospective data • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMN2

From Genes to Function: Clinical Experience with the Effectiveness and Safety of Risdiplam and Nusinersen in Spinal Muscular Atrophy. (PubMed, Iran J Child Neurol) - "No severe side effects were experienced and only a few patients reported headaches, and backaches following Nusinersen. both Risdiplam and Nusinersen led to significant improvements in motor function; however, based on cost-effectiveness considerations, we recommend Risdiplam."

Journal • Back Pain • Genetic Disorders • Movement Disorders • Muscular Atrophy • Pain • Rare Diseases • SMA4 • SMN1 • SMN2

Gene therapy benefits in a small cohort of symptomatic 5q spinal muscular atrophy patients and real world pediatric outcomes. (PubMed, J Pediatr (Rio J)) - "In this small and heterogeneous cohort, gene therapy after symptom onset was primarily associated with clinical stabilization and limited motor milestone acquisition, while established respiratory and nutritional impairments persisted. These results emphasize the need for realistic treatment counseling and reinforce the importance of early diagnosis."

Journal • Real-world evidence • Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Pediatrics • Rare Diseases • Respiratory Diseases

Detection of antisense oligonucleotides from biological samples by ligase detection reaction using T4 RNA ligase 2. (PubMed, Biotechniques) - "The LDR was applied to detect a nusinersen-based ASO, an 18-mer 2'-O-methoxyethyl-modifiedoligonucleotide with phosphorothioate linkages...The method was further applied to determine ASO levels in plasma and spinal tissue following intrathecal injection in mice. These results demonstrated that LDR using T4Rnl2 was a simple and sensitive approach for detecting ASOs in biological samples."

Journal

Therapeutic strategies for spinal muscular atrophy: the history and future perspective. (PubMed, Front Hum Neurosci) - "The FDA approval of nusinersen, an antisense oligonucleotide targeting SMN2 splicing, in 2016 marked the first disease-modifying therapy, followed by the gene replacement therapy onasemnogene abeparvovec in 2019 and the orally administered small-molecule splicing modifier risdiplam in 2020...Finally, we address future directions encompassing precision medicine, next-generation gene editing, and biomarker-driven trial design. While SMA has been transformed from a fatal childhood disorder to a treatable condition, a definitive cure for all patients remains the goal of ongoing and future research."

Journal • Review • CNS Disorders • Gene Therapies • Genetic Disorders • Inflammation • Movement Disorders • Muscular Atrophy • Rare Diseases • NEFL • PLS3 • PTEN • SMA4 • SMN1 • SMN2

Effects of newborn screening and nusinersen on survival and functional outcomes in spinal muscular atrophy with two SMN2 copies: A nationwide multicentre real-world study from Turkey. (PubMed, Eur J Paediatr Neurol) - "NBS program fundamentally altered the clinical trajectory of SMA Type 1 in infants with two SMN2 copies in the present cohort. Pre-symptomatic treatment in the NBS cohort supports sustained motor development and preserves bulbar and respiratory functions, underscoring the importance of minimising delays between birth, diagnosis, and treatment initiation."

Journal • Real-world evidence • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMN2

A Study to Learn About the Long-Term Safety of Higher Doses of Nusinersen (BIIB058) Given as Injections to Participants With Spinal Muscular Atrophy (SMA) Who Took Part in an Earlier Nusinersen Trial (ONWARD) (clinicaltrials.gov) - P3 | N=115 | Completed | Sponsor: Biogen | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Longitudinal Dosing Patterns and Treatment Costs Among Patients with Spinal Muscular Atrophy Initiating Nusinersen and Risdiplam. (PubMed, Adv Ther) - P | "Nusinersen and risdiplam persistence declined over time. Among patients remaining on their index therapy, both treatments had high long-term costs, highlighting the substantial and ongoing financial burden of chronic SMA therapies and the need for real-world evidence to inform healthcare planning."

Journal • CNS Disorders • Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Brain Morphological Alterations in Adults with Spinal Muscular Atrophy Types 2 and 3: A CAT12-Derived Region-Based and Surface-Based Morphometry Study. (PubMed, J Clin Med) - "MRI examinations were performed before initiation of disease-modifying therapy or during the early loading phase of intrathecal nusinersen treatment, with a maximum exposure of two months and no more than three doses before MRI...These findings are consistent with the concept that SMA may extend beyond lower motor neuron degeneration. Larger longitudinal multimodal studies are warranted to validate these observations and clarify their clinical significance."

Journal • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases