ArticleAmerican journal of human genetics2019
NCALD Antisense Oligonucleotide Therapy in Addition to Nusinersen further Ameliorates Spinal Muscular Atrophy in Mice.
Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Combination therapies in spinal muscular atrophy: a systematic review.European journal of pediatrics · 2025Pooled it
- Organ-specific redox imbalances in spinal muscular atrophy mice are partially rescued by SMN antisense oligonucleotides.FEBS letters · 2026Article
- Survival motor neuron protein-independent amelioration of spinal muscular atrophy by pharmacological inhibition of c-Jun-NHBrain communications · 2026Article
- Therapeutic strategies for spinal muscular atrophy: the history and future perspective.Frontiers in human neuroscience · 2026Review
- Identification of p38 MAPK inhibition as a neuroprotective strategy for combinatorial SMA therapy.EMBO molecular medicine · 2025Article
- The effect of coadministration of D156844 and AR42 (REC-2282) on the survival and motor phenotype of mice with spinal muscular atrophy.Scientific reports · 2025Article
- Isolation and Identification of Inter-Correlated Genes from the Invasive Sun CoralsInternational journal of molecular sciences · 2025Article
- Concepts of Regeneration for Spinal Diseases in 2023.International journal of molecular sciences · 2023Article
- The impact of Yiwei decoction on the LncRNA and CircRNA regulatory networks in premature ovarian insufficiency.Heliyon · 2023Article
- Long-TermInternational journal of molecular sciences · 2023Article
- Gene Therapy in ALS and SMA: Advances, Challenges and Perspectives.International journal of molecular sciences · 2023Review
- Autophagy in spinal muscular atrophy: from pathogenic mechanisms to therapeutic approaches.Frontiers in cellular neuroscience · 2023Review
- Investigation on the Effects of Modifying Genes on the Spinal Muscular Atrophy Phenotype.Global medical genetics · 2022Article
- Spinal muscular atrophy.Nature reviews. Disease primers · 2022Review
- Post-genomic platform for development of oligonucleotide vaccines against RNA viruses: diamond cuts diamond.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Article
- Recent research on the treatment of spinal muscular atrophy.Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2022Review
- Therapy development for spinal muscular atrophy: perspectives for muscular dystrophies and neurodegenerative disorders.Neurological research and practice · 2022Review
- Spinal muscular atrophy: From approved therapies to future therapeutic targets for personalized medicine.Cell reports. Medicine · 2021Review
- In Search of a Cure: The Development of Therapeutics to Alter the Progression of Spinal Muscular Atrophy.Brain sciences · 2021Review
- AAV9-DOK7 gene therapy reduces disease severity in SmnBiochemical and biophysical research communications · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spinal muscular atrophy (SMA) is a neuromuscular disease causing the most frequent genetic childhood lethality. Recently, nusinersen, an antisense oligonucleotide (ASO) that corrects SMN2 splicing and thereby increases full-length SMN protein, has been approved by the FDA and EMA for SMA therapy. However, the administration of nusinersen in severe and/or post-symptomatic SMA-affected individuals is insufficient to counteract the disease. Therefore, additional SMN-independent therapies are needed to support the function of motoneurons and neuromuscular junctions. We recently identified asymptomatic SMN1-deleted individuals who were protected against SMA by reduced expression of neurocalcin delta (NCALD). NCALD reduction is proven to be a protective modifier of SMA across species, including worm, zebrafish, and mice. Here, we identified Ncald-ASO3-out of 450 developed Ncald ASOs-as the most efficient and non-toxic ASO for the CNS, by applying a stepwise screening strategy in cortical neurons and adult and neonatal mice. In a randomized-blinded preclinical study, a single subcutaneous low-dose SMN-ASO and a single intracerebroventricular Ncald-ASO3 or control-ASO injection were presymptomatically administered in a severe SMA mouse model. NCALD reduction of >70% persisted for about 1 month. While low-dose SMN-ASO rescues multiorgan impairment, additional NCALD reduction significantly ameliorated SMA pathology including electrophysiological and histological properties of neuromuscular junctions and muscle at P21 and motoric deficits at 3 months. The present study shows the additional benefit of a combinatorial SMN-dependent and SMN-independent ASO-based therapy for SMA. This work illustrates how a modifying gene, identified in some asymptomatic individuals, helps to develop a therapy for all SMA-affected individuals.
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Registered trials
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