4.5 Review

Therapeutic interventions for spinal muscular atrophy: preclinical and early clinical development opportunities

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Systematic literature review of the economic burden of spinal muscular atrophy and economic evaluations of treatments

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Summary: The review summarizes studies on the cost of caring for spinal muscular atrophy (SMA) patients and economic evaluations of treatments, revealing a substantial cost burden of standard care for SMA patients and high cost-effectiveness ratios of approved drugs in post-symptomatic patients at current prices. Additional prospective and independent economic studies in pre- and post-symptomatic patients are needed due to the limited number of conducted studies.

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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.

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Article Gastroenterology & Hepatology

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

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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.

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Reldesemtiv in Patients with Spinal Muscular Atrophy: a Phase 2 Hypothesis-Generating Study

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Summary: This study demonstrated that reldesemtiv may offer clinical benefit for patients with SMA, especially showing significant improvements in 6-minute walk distance and maximum expiratory pressure.

NEUROTHERAPEUTICS (2021)

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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.

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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.

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Limited Assessment of Respiratory Muscle Response to Nusinersen Treatment in Infants with Spinal Muscular Atrophy Reply

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

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Drosophila SMN2 minigene reporter model identifies moxifloxacin as a candidate therapy for SMA

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FASEB JOURNAL (2020)

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Myostatin inhibition in combination with antisense oligonucleotide therapy improves outcomes in spinal muscular atrophy

Haiyan Zhou et al.

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

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Nusinersen treatment of spinal muscular atrophy: current knowledge and existing gaps

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Newborn screening for SMA in Southern Belgium

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Systemic nature of spinal muscular atrophy revealed by studying insurance claims

Scott L. Lipnick et al.

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Salbutamol modifies the neuromuscular junction in a mouse model of ColQ myasthenic syndrome

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NCALD Antisense Oligonucleotide Therapy in Addition to Nusinersen further Ameliorates Spinal Muscular Atrophy in Mice

Laura Torres-Benito et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2019)

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Nusinersen in type 1 spinal muscular atrophy: Twelve-month real-world data

Marika Pane et al.

ANNALS OF NEUROLOGY (2019)

Editorial Material Clinical Neurology

Discrepancy in redetermination of SMN2 copy numbers in children with SMA

David Christof Schorling et al.

NEUROLOGY (2019)

Article Medicine, Research & Experimental

Age-dependent SMN expression in disease-relevant tissue and implications for SMA treatment

Daniel M. Ramos et al.

JOURNAL OF CLINICAL INVESTIGATION (2019)

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 Cell & Tissue Engineering

A SMN2 Splicing Modifier Rescues the Disease Phenotypes in an In Vitro Human Spinal Muscular Atrophy Model

Ye Seul Son et al.

STEM CELLS AND DEVELOPMENT (2019)

Article Biochemistry & Molecular Biology

Specific inhibition of myostatin activation is beneficial in mouse models of SMA therapy

Kimberly K. Long et al.

HUMAN MOLECULAR GENETICS (2019)

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One Year of Newborn Screening for SMA - Results of a German Pilot Project

Katharina Vill et al.

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The role of survival motor neuron protein (SMN) in protein homeostasis

Helena Chaytow et al.

CELLULAR AND MOLECULAR LIFE SCIENCES (2018)

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Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy

E. Mercuri et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

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Nusinersen in patients older than 7 months with spinal muscular atrophy type 1 A cohort study

Karolina Aragon-Gawinska et al.

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Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy

J. R. Mendell et al.

NEW ENGLAND JOURNAL OF MEDICINE (2017)

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Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy

R. S. Finkel et al.

NEW ENGLAND JOURNAL OF MEDICINE (2017)

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Reloading Promotes Recovery of Disuse Muscle Loss by Inhibiting TGF Pathway Activation in Rats After Hind Limb Suspension

Jinyue Wang et al.

AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION (2017)

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Securinine enhances SMN2 exon 7 inclusion in spinal muscular atrophy cells

Yu-Chia Chen et al.

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The Power of Human Protective Modifiers: PLS3 and CORO1C Unravel Impaired Endocytosis in Spinal Muscular Atrophy and Rescue SMA Phenotype

Seyyedmohsen Hosseinibarkooie et al.

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Vascular Defects and Spinal Cord Hypoxia in Spinal Muscular Atrophy

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SMN2 splice modulators enhance U1-pre-mRNA association and rescue SMA mice

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Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trial

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Treatment of sporadic inclusion body myositis with bimagrumab

Anthony A. Amato et al.

NEUROLOGY (2014)

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SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy

Nikolai A. Naryshkin et al.

SCIENCE (2014)

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Spinal Muscular Atrophy: New Findings for an Old Pathology

Daniele Bottai et al.

BRAIN PATHOLOGY (2013)

Article Biochemistry & Molecular Biology

Arrhythmia and cardiac defects are a feature of spinal muscular atrophy model mice

Christopher R. Heier et al.

HUMAN MOLECULAR GENETICS (2010)

Article Clinical Neurology

The Developmental Pattern of Myotubes in Spinal Muscular Atrophy Indicates Prenatal Delay of Muscle Maturation

Rebeca Martinez-Hernandez et al.

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A phase I/II trial of MYO-029 in adult subjects with muscular dystrophy

Kathryn R. Wagner et al.

ANNALS OF NEUROLOGY (2008)

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Brief report -: Myostatin mutation associated with gross muscle hypertrophy in a child

M Schuelke et al.

NEW ENGLAND JOURNAL OF MEDICINE (2004)