Zolgensma (onasemnogene abeparvovec-xioi) / Novartis, REGENXBIO - LARVOL DELTA

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

SMA-REAL: A Real-World Medical Chart Review of Spinal Muscular Atrophy Patients Treated With Onasemnogene Abeparvovec in Saudi Arabia (clinicaltrials.gov) - P=N/A | N=6 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Real-world evidence • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

MTE #24: Gene Therapies and Hepatotoxicity (Ticketed) (AASLD 2026) - "Multiple gene therapies have been approved in recent years by the US Food and Drug Administration (FDA) for a variety of inherited disorders, including: Duchenne muscular dystrophy (delandistrogene moxeparvovec-rokl, 2023) Hemophilia A (valoctocogene roxaparvovec-rvox, 2023) Hemophilia B (etranacogene dezaparvovec-drlb, 2022; fidanacogene elaparvovec-dzkt, 2024) Spinal muscular atrophy (onasemnogene abeparvovec-brve, 2025) Sickle cell disease (exagamglogene autotemcel, 2023)...Identify clinically available AAV gene therapy treatments. Discuss ways to identify and potentially mitigate hepatotoxicity, and to optimize care for patients and study participants receiving AAV gene therapy."

Gene therapy • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Hepatology • Liver Failure • Movement Disorders • Muscular Atrophy • Muscular Dystrophy • Rare Diseases • Sickle Cell Disease

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

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

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

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

289th ENMC international workshop: assessing and managing emerging AAV related toxicities after gene therapy for neuromuscular disorders, 26 - 28 September 2025, Hoofddorp, The Netherlands. (PubMed, Neuromuscul Disord) - "Adeno-associated virus (AAV) mediated gene therapies has emerged as a potentially transformative treatment approaches for neuromuscular disorders, with two FDA-approved products now in widespread clinical use: onasemnogene abeparvovec (Zolgensma) for spinal muscular atrophy and delandistrogene moxeparvovec-rokl (Elevidys) for Duchenne Muscular Dystrophy...Emerging toxicities, including capillary leak syndrome, endothelial and dorsal root ganglia injuries, were reviewed alongside corresponding preclinical data from non-human primates. Participants agreed on the need to harmonize standard operating procedures, clinical guidelines, and data-sharing practices, and endorsed collaborative initiatives to proactively address critical gaps and unresolved key questions through a patient-centered framework."

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

Delphi consensus on gene therapy of spinal muscular atrophy with onasemnogene abeparvovec in Germany, Austria and Switzerland - part II - expert based recommendations for surveillance and management of side-effects. (PubMed, J Neuromuscul Dis) - "Delphi-based expert recommendations, developed in co-creation with patient representatives, provide a framework to minimize complications associated with gene therapy and establish the basis for standardized post-marketing data collections. The methodology used in this Delphi-consensus-group can serve as a blueprint for future gene therapy approvals."

Adverse events • Journal • Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Genetic susceptibility to thrombotic microangiopathy in a 10-month-old patient with SMA type 1: a caveat for gene therapy eligibility. (PubMed, Neuromuscul Disord) - "The multidisciplinary team considered the patient at high risk and OA was withheld to prevent a potentially fatal TMA event. This case highlights how systematic complement screening prior to gene therapy may help identify high-risk individuals."

Journal • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Gene Therapies • Genetic Disorders • Infectious Disease • Movement Disorders • Muscular Atrophy • Nephrology • Rare Diseases • 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

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

STELLAR-2: A Study to Learn About the Safety and Effects of Salanersen (BIIB115) When Given to Babies With Spinal Muscular Atrophy (SMA) Who Were Previously Treated With Onasemnogene Abeparvovec (clinicaltrials.gov) - P3 | N=42 | Recruiting | Sponsor: Biogen | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • Plasma NfL • SMN2

Compound muscle action potential amplitudes in newborn screen positive spinal muscular atrophy. (PubMed, Clin Neurophysiol) - "CMAP assessment is a useful adjunct in the evaluation of infants identified through SMA NBS."

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

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

SMA-REAL: A Real-World Medical Chart Review of Spinal Muscular Atrophy Patients Treated With Onasemnogene Abeparvovec in Saudi Arabia (clinicaltrials.gov) - P=N/A | N=6 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New trial • Real-world evidence • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Trends in the Engineering of Adeno-Associated Virus (AAV) for Precision Gene Delivery to the Central Nervous System (CNS). (PubMed, Int J Mol Sci) - "Despite these challenges, our understanding of AAV structure and technological advances continue to enable researchers to develop innovative strategies that have resulted in groundbreaking, FDA-approved therapeutic products now available for Leber congenital amaurosis (LCA) (Luxturna®), spinal muscular atrophy (SMA) (Zolgensma®), and the two recent gene therapy products for aromatic L-amino acid decarboxylase (AADC) deficiency, Kebilidi® and Upstaza®, which currently hold FDA and EMA approval, respectively. This review aims to highlight recent advances in the field of AAV gene therapy for neurological disorders, identify research gaps, and suggest areas for future investigation to enable potential breakthroughs particularly in neurodegenerative, neurodevelopmental, and neuromuscular disorders. We foresee that more tissue- and cell-specific AAV vectors designed using AI-powered platforms will emerge to precisely and efficiently target specific brain..."

Journal • Review • Alzheimer's Disease • CNS Disorders • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Movement Disorders • Muscular Atrophy • Parkinson's Disease • Rare Diseases

Spinal muscular atrophies: From molecular mechanisms to therapeutic breakthroughs (EAN 2026) - "Splicing modulators, including nusinersen and risdiplam, represent groundbreaking RNA-targeted approaches that enhance SMN2 exon 7 inclusion to increase functional SMN protein production...Patient selection criteria, biomarkers for treatment response monitoring, and individualized treatment algorithms based on SMN2 copy number and disease severity will be discussed. Finally, new and emerging therapies, including next-generation gene therapies, combination treatment strategies, and neuroprotective approaches targeting muscle and neuronal pathways beyond SMN restoration, will be explored as the future frontier of SMA management."

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

Vulnerability, protection and fairness: ethical and regulatory limits in small-N gene therapy trials. (PubMed, Trials) - "Current gene therapy trial frameworks largely succeed in supporting methodological flexibility for ultra-rare conditions but insufficiently operationalize fair inclusion. Ethical concerns arise not because participant protections are excessive, but because the burdens associated with necessary scientific and regulatory requirements may disproportionately affect patients facing structural disadvantages. Ensuring justice in ultra-rare gene therapy research requires extending proportionate, risk-based approaches beyond evidence generation to include the identification and mitigation of foreseeable barriers to participation."

Journal • Gene Therapies • Rare Diseases

SPECTRUM: Long-term Follow-up of Patients With Spinal Muscular Atrophy Treated With OAV101 in Clinical Trials (clinicaltrials.gov) - P3 | N=20 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=175 ➔ 20 | Trial primary completion date: Sep 2030 ➔ Apr 2031

Enrollment change • Enrollment closed • Trial primary completion date • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Clinical Outcomes of SMA Type 1 Patients Treated With Zolgensma in Brazil Public Health System (ICNMD 2026) - "Early diagnosis of SMA is a critical determinant of therapeutic efficacy, as rapid and irreversible motor neuron loss occurs early in the disease course. Identification of affected infants—particularly through newborn screening—enables timely initiation of treatment before significant neuromuscular impairment, thereby optimizing motor outcomes. In this context, the availability of Zolgensma® within the Brazilian Unified Health System represents a major advance in public health policy for rare diseases."

Clinical • Clinical data • CNS Disorders • Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Characterisation of Anti-AAV9 Seropositivity in Zolgensma Treated SMA Patients (ICNMD 2026) - "Together, these findings highlight the critical role of IgG1-driven complement activation in AAV9 immunogenicity and establish the utility of integrating subclass-specific serology with complement and serum inflammatory profiling into precision risk stratification frameworks. Our platform advances the field by enabling safer, more individualized gene therapy delivery through mechanistically informed monitoring and intervention strategies."

Clinical • Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • APOA1 • IGF2

Long-Term Real-World Outcomes Following Onasemnogene Abeparvovec Monotherapy for Patients With SMA: Updated Findings From RESTORE (ICNMD 2026) - "These data, while limited to patients treated with OA as monotherapy, indicate therapeutic benefit for up to 5 years post-dosing, providing further evidence for OA as a durable treatment for patients with SMA."

Clinical • Monotherapy • Real-world • Real-world evidence • CNS Disorders • Gene Therapies • Genetic Disorders • Hematological Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • Thrombocytopenia • SMN2

Adeno-Associated Virus Gene Therapy for Spinal Muscular Atrophy Induces Hepatotoxicity via Cytokine and Macrophage Activation. (PubMed, Liver Int) - "Our findings clarify the immunological basis underlying hepatotoxicity in patients after AAV gene therapy. Furthermore, these findings provide a rationale for using various immunosuppressants or chemokine blockers in patients exhibiting severe adverse effects."

Journal • Dyslipidemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Hypertriglyceridemia • Movement Disorders • Muscular Atrophy • Rare Diseases • Thrombocytopenia

ANALYSIS OF ANTHROPOMETRIC PARAMETERS AND SWALLOWING FUNCTION IN CHILDREN WITH TYPE I SPINAL MUSCULAR ATROPHY UNDER DISEASE-MODIFYING THERAPY (ESPGHAN 2026) - "Ninety-three percent (n = 28) were receiving nusinersen as DMT, and 11 were also treated with onasemnogene abeparvovec...Nutritionally, many children needed gastrostomy and/or supplements, and frequent reflux and constipation highlight the need for comprehensive gastrointestinal management. Contact e-mail address [email protected]"

Clinical • Constipation • Gastroenterology • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases