4.6 Review

Recombinant Adeno-Associated Virus Serotype 9 Gene Therapy in Spinal Muscular Atrophy

Related references

Note: Only part of the references are listed.
Article Clinical Neurology

Clinical and radiological profile of patients with spinal muscular atrophy type 4

P. V. S. Souza et al.

Summary: This study identified a cohort of 20 patients with SMA type 4 in a Brazilian cohort of 227 SMA patients. The most common clinical symptom was limb-girdle muscle weakness, with absent tendon reflexes in 90% of patients and fasciculations in 45% of patients. The majority of patients (80%) had the homozygous deletion of exon 7 in the SMN1 gene, with 60% of them showing four copies of the SMN2 gene.

EUROPEAN JOURNAL OF NEUROLOGY (2021)

Review Biotechnology & Applied Microbiology

Current Clinical Applications of In Vivo Gene Therapy with AAVs

Jerry R. Mendell et al.

Summary: Hereditary diseases are caused by gene mutations, affecting millions of Americans, and gene therapy using adeno-associated virus (AAV) has shown promise in treating these diseases. Five treatments have been approved for commercialization, with many more in clinical trials, showcasing the potential of gene therapy in treating a wide range of genetic disorders.

MOLECULAR THERAPY (2021)

Article Clinical Neurology

Feeding difficulties in children and adolescents with spinal muscular atrophy type 2

Renske Wadman et al.

Summary: Feeding difficulties are common in spinal muscular atrophy type 2 patients, which may lead to weight loss and malnutrition, requiring enteral feeding. Gastrostomy feeding significantly improves chest infections and nutritional status in these patients.

NEUROMUSCULAR DISORDERS (2021)

Article Genetics & Heredity

Executive function is inversely correlated with physical function: the cognitive profile of adult Spinal Muscular Atrophy (SMA)

Lucas Mix et al.

Summary: This study found that adult SMA patients showed cognitive abilities within the normal range across all assessed domains, with no significant differences compared to neurologically healthy controls. Reduction of SMN protein did not appear to have a negative impact on cognitive function. Executive functions were the only cognitive domain correlated with disease severity, suggesting a potential role in adapting to physical restrictions in SMA and warranting further research.

ORPHANET JOURNAL OF RARE DISEASES (2021)

Article Clinical Neurology

Natural history of Type 2 and 3 spinal muscular atrophy: 2-year NatHis-SMA study

Melanie Annoussamy et al.

Summary: Upper limb activity and strength began to significantly decline at 12 months and continued to decrease at 24 months, while motor function scores significantly declined at 24 months. Pulmonary function significantly declined at 12 months, while blood SMN protein levels remained stable at 12 and 24 months.

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY (2021)

Article Neurosciences

Dual SMN inducing therapies can rescue survival and motor unit function in symptomatic increment 7SMA mice

Kaitlyn M. Kray et al.

Summary: Spinal muscular atrophy (SMA) is a genetic disease characterized by SMN protein deficiency leading to motor neuron loss and muscle atrophy. Increasing SMN levels before symptom onset provides the greatest therapeutic benefit, but treatment after motor neuron loss has occurred also shows effectiveness.

NEUROBIOLOGY OF DISEASE (2021)

Article Gastroenterology & Hepatology

Hepatotoxicity following administration of onasemnogene abeparvovec (AVXS-101) for the treatment of spinal muscular atrophy

Deepa Chand et al.

Summary: This study focuses on the risk of liver injury associated with OA in the treatment of SMA and provides guidance on its management. Analysis of data from 325 patients receiving OA treatment showed elevated liver function test results in some patients. Most patients mitigated these adverse effects through prophylactic prednisolone treatment.

JOURNAL OF HEPATOLOGY (2021)

Article Clinical Neurology

Nusinersen treatment of spinal muscular atrophy type 1-results of expanded access programme in Poland

Sandra Modrzejewska et al.

Summary: This study aimed to evaluate the effects of nusinersen therapy in Polish children with SMA type 1. The results showed that the treatment could improve patients' motor function and survival status, with patients having different gene copy numbers showing varying therapeutic effects.

NEUROLOGIA I NEUROCHIRURGIA POLSKA (2021)

Article Medicine, General & Internal

Risdiplam in Type 1 Spinal Muscular Atrophy

Giovanni Baranello et al.

Summary: In a study involving 21 infants with type 1 spinal muscular atrophy, treatment with oral risdiplam resulted in increased levels of functional SMN protein in the blood. Infants in the high-dose group were more likely to sit without support for at least 5 seconds, and the higher dose of risdiplam was selected for the second part of the study.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

Article Pediatrics

Thrombotic Microangiopathy Following Onasemnogene Abeparvovec for Spinal Muscular Atrophy: A Case Series

Deepa H. Chand et al.

Summary: Spinal muscular atrophy is treated with onasemnogene abeparvovec, but it can lead to drug-induced thrombotic microangiopathy in some infants. Early recognition and treatment of this complication may reduce mortality and morbidity.

JOURNAL OF PEDIATRICS (2021)

Article Clinical Neurology

Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial

John W. Day et al.

Summary: The study evaluated the safety and efficacy of onasemnogene abeparvovec gene therapy in symptomatic patients with infantile-onset spinal muscular atrophy. Results showed that patients achieved independent sitting and survival rates without permanent ventilation at certain time points, with a favorable benefit-risk profile supporting the use of onasemnogene abeparvovec for treatment of this condition.

LANCET NEUROLOGY (2021)

Article Neurosciences

Gain of toxic function by long-term AAV9-mediated SMN overexpression in the sensorimotor circuit

Meaghan Van Alstyne et al.

Summary: This study demonstrates that long-term use of AAV9-SMN gene therapy in mice can lead to motor dysfunction and neuronal loss through protein aggregation. Overexpression of SMN interferes with RNA regulation and triggers SMA-like pathogenic events through toxic gain-of-function mechanisms. These findings suggest caution in the long-term safety of treating individuals with SMA with AAV9-SMN.

NATURE NEUROSCIENCE (2021)

Article Genetics & Heredity

Newborn screening for spinal muscular atrophy in Germany: clinical results after 2 years

Katharina Vill et al.

Summary: The study assessed the impact of genetic newborn screening for spinal muscular atrophy (SMA) on disease outcomes, showing that early diagnosis and treatment of SMA are crucial in preventing major disability, with newborn screening results consistent with known incidence in Germany. Timely SMA-specific treatment significantly improves neurodevelopmental outcomes.

ORPHANET JOURNAL OF RARE DISEASES (2021)

Article Genetics & Heredity

Observation of the natural course of type 3 spinal muscular atrophy: data from the polish registry of spinal muscular atrophy

Anna Lusakowska et al.

Summary: This study investigates patients included in the Polish Registry of SMA, focusing on the course of type 3 SMA before the availability of disease-modifying treatments. The results show that SMN2 copy number, sex, and age of disease onset strongly affect the age of onset and ambulation in SMA3. Data from this study can provide valuable information for treatment decisions.

ORPHANET JOURNAL OF RARE DISEASES (2021)

Article Clinical Neurology

Five-Year Extension Results of the Phase 1 START Trial of Onasemnogene Abeparvovec in Spinal Muscular Atrophy

Jerry R. Mendell et al.

Summary: This ongoing study evaluates the long-term safety and effectiveness of onasemnogene abeparvovec gene replacement therapy in infants with SMA type 1. The therapeutic dose showed sustained clinical benefits for patients with no need for permanent ventilation up to 6 years of age.

JAMA NEUROLOGY (2021)

Article Clinical Neurology

Combination therapy with onasemnogene and risdiplam in spinal muscular atrophy type 1

Kelly F. Oechsel et al.

Summary: Combination therapy with onasemnogene and risdiplam in patients with spinal muscular atrophy (SMA) is well-tolerated, with patients experiencing objective and subjective improvement. Further large prospective trials are needed to determine the comparative efficacy of dual therapy over monotherapy, and to identify rare adverse events associated with combination therapy.

MUSCLE & NERVE (2021)

Article Clinical Neurology

Sitting in patients with spinal muscular atrophy type 1 treated with nusinersen

Karolina Aragon-Gawinska et al.

DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY (2020)

Review Genetics & Heredity

Longitudinal natural history of type I spinal muscular atrophy: a critical review

Eugenio Mercuri et al.

ORPHANET JOURNAL OF RARE DISEASES (2020)

Article Clinical Neurology

European ad-hoc consensus statement on gene replacement therapy for spinal muscular atrophy

Janbernd Kirschner et al.

EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY (2020)

Article Clinical Neurology

Clinical Variability in Spinal Muscular Atrophy TypeIII

Giorgia Coratti et al.

ANNALS OF NEUROLOGY (2020)

Article Clinical Neurology

Combination molecular therapies for type 1 spinal muscular atrophy

Yohei Harada et al.

MUSCLE & NERVE (2020)

Article Pharmacology & Pharmacy

Risdiplam: First Approval

Sohita Dhillon

DRUGS (2020)

Review Clinical Neurology

Spinal muscular atrophy - insights and challenges in the treatment era

Eugenio Mercuri et al.

NATURE REVIEWS NEUROLOGY (2020)

Article Clinical Neurology

Impact of a national population-based carrier-screening program on spinal muscular atrophy births

Sharon Aharoni et al.

NEUROMUSCULAR DISORDERS (2020)

Article Pediatrics

Gene Therapy for Spinal Muscular Atrophy: Safety and Early Outcomes

Megan A. Waldrop et al.

PEDIATRICS (2020)

Article Clinical Neurology

Feeding and Swallowing Problems in Infants with Spinal Muscular Atrophy Type 1: an Observational Study

A. M. B. van der Heul et al.

JOURNAL OF NEUROMUSCULAR DISEASES (2020)

Article Health Care Sciences & Services

Clinical Evidence Supporting Early Treatment Of Patients With Spinal Muscular Atrophy: Current Perspectives

Tamara Dangouloff et al.

THERAPEUTICS AND CLINICAL RISK MANAGEMENT (2019)

Article Clinical Neurology

Clinical phenotypes and trajectories of disease progression in type 1 spinal muscular atrophy

Roberto De Sanctis et al.

NEUROMUSCULAR DISORDERS (2018)

Letter Medicine, General & Internal

Therapy for Spinal Muscular Atrophy

Heather T. Whittaker et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

Article Medicine, General & Internal

Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy

E. Mercuri et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

Article Medicine, General & Internal

Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy

J. R. Mendell et al.

NEW ENGLAND JOURNAL OF MEDICINE (2017)

Article Medicine, General & Internal

Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy

R. S. Finkel et al.

NEW ENGLAND JOURNAL OF MEDICINE (2017)

Article Clinical Neurology

Sleep disorders in spinal muscular atrophy

Maria C. Pera et al.

SLEEP MEDICINE (2017)

Article Clinical Neurology

Natural history of infantile-onset spinal muscular atrophy

Stephen J. Kolb et al.

ANNALS OF NEUROLOGY (2017)

Review Clinical Neurology

Emerging Therapies and Challenges in Spinal Muscular Atrophy

Michelle A. Farrar et al.

ANNALS OF NEUROLOGY (2017)

Article Biochemistry & Molecular Biology

Large-Scale Production of Adeno-Associated Viral Vector Serotype-9 Carrying the Human Survival Motor Neuron Gene

Afrooz Rashnonejad et al.

MOLECULAR BIOTECHNOLOGY (2016)

Article Biochemistry & Molecular Biology

Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of > 72 400 specimens

Elaine A. Sugarman et al.

EUROPEAN JOURNAL OF HUMAN GENETICS (2012)

Article Biochemistry & Molecular Biology

Intravenous scAAV9 delivery of a codon-optimized SMN1 sequence rescues SMA mice

Elisa Dominguez et al.

HUMAN MOLECULAR GENETICS (2011)

Article Cell Biology

Antisense Oligonucleotides Delivered to the Mouse CNS Ameliorate Symptoms of Severe Spinal Muscular Atrophy

Marco A. Passini et al.

SCIENCE TRANSLATIONAL MEDICINE (2011)

Article Biochemistry & Molecular Biology

Early heart failure in the SMNΔ7 model of spinal muscular atrophy and correction by postnatal scAAV9-SMN delivery

Adam K. Bevan et al.

HUMAN MOLECULAR GENETICS (2010)

Article Biotechnology & Applied Microbiology

Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN

Kevin D. Foust et al.

NATURE BIOTECHNOLOGY (2010)

Article Biotechnology & Applied Microbiology

Intravenous Administration of Self-complementary AAV9 Enables Transgene Delivery to Adult Motor Neurons

Sandra Duque et al.

MOLECULAR THERAPY (2009)

Article Biotechnology & Applied Microbiology

Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes

Kevin D. Foust et al.

NATURE BIOTECHNOLOGY (2009)

Review Neurosciences

Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick?

Arthur H. M. Burghes et al.

NATURE REVIEWS NEUROSCIENCE (2009)

Article Clinical Neurology

The Hammersmith functional score correlates with the SMN2 copy number:: A multicentric study

F. D. Tiziano et al.

NEUROMUSCULAR DISORDERS (2007)

Article Clinical Neurology

Natural history of denervation in SMA:: Relation to age, SMN2 copy number, and function

KJ Swoboda et al.

ANNALS OF NEUROLOGY (2005)

Article Clinical Neurology

Intelligence and cognitive function in children and adolescents with spinal muscular atrophy

A von Gontard et al.

NEUROMUSCULAR DISORDERS (2002)

Article Genetics & Heredity

Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2

MD Mailman et al.

GENETICS IN MEDICINE (2002)