ArticleJCI insight2016
ML372 blocks SMN ubiquitination and improves spinal muscular atrophy pathology in mice.
Article in JCI insight, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 3 syntheses or guidelines pooled it, 21 citations in OpenAlex.
- A standardized framework resolves ambiguity in motor neuron loss across neurodegenerative diseases.Acta neuropathologica communications · 2026Pooled it
- Drug treatment for spinal muscular atrophy types II and III.The Cochrane database of systematic reviews · 2020Pooled it
- Drug treatment for spinal muscular atrophy type I.The Cochrane database of systematic reviews · 2019Pooled it
- A standardized framework resolves ambiguity in motor neuron loss across neurodegenerative diseases.bioRxiv : the preprint server for biology · 2026Article
- 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
- Transcriptional reprogramming in SMA mouse hearts reveals signatures of early heart failure and dysregulated calcium signaling.Human molecular genetics · 2025Article
- Evaluation of the orally bioavailable 4-phenylbutyrate-tethered trichostatin A analogue AR42 in models of spinal muscular atrophy.Scientific reports · 2023Article
- SMN post-translational modifications in spinal muscular atrophy.Frontiers in cellular neuroscience · 2023Review
- A combinatorial approach increases SMN level in SMA model mice.Human molecular genetics · 2022Article
- Hyper-SUMOylation of SMN induced by SENP2 deficiency decreases its stability and leads to spinal muscular atrophy-like pathology.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Survival motor neuron deficiency slows myoblast fusion through reduced myomaker and myomixer expression.Journal of cachexia, sarcopenia and muscle · 2021Article
- Spinal muscular atrophy: From approved therapies to future therapeutic targets for personalized medicine.Cell reports. Medicine · 2021Review
- A high-throughput genome-wide RNAi screen identifies modifiers of survival motor neuron protein.Cell reports · 2021Article
- The Ubiquitin Proteasome System in Neuromuscular Disorders: Moving Beyond Movement.International journal of molecular sciences · 2020Review
- Intraperitoneal delivery of a novel drug-like compound improves disease severity in severe and intermediate mouse models of Spinal Muscular Atrophy.Scientific reports · 2019Article
- The role of survival motor neuron protein (SMN) in protein homeostasis.Cellular and molecular life sciences : CMLS · 2018Review
- UBA1/GARS-dependent pathways drive sensory-motor connectivity defects in spinal muscular atrophy.Brain : a journal of neurology · 2018Article
- Advances in therapy for spinal muscular atrophy: promises and challenges.Nature reviews. Neurology · 2018Review
- Overview of Current Drugs and Molecules in Development for Spinal Muscular Atrophy Therapy.Drugs · 2018Review
- Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease and one of the leading inherited causes of infant mortality. SMA results from insufficient levels of the survival motor neuron (SMN) protein, and studies in animal models of the disease have shown that increasing SMN protein levels ameliorates the disease phenotype. Our group previously identified and optimized a new series of small molecules, with good potency and toxicity profiles and reasonable pharmacokinetics, that were able to increase SMN protein levels in SMA patient-derived cells. We show here that ML372, a representative of this series, almost doubles the half-life of residual SMN protein expressed from the SMN2 locus by blocking its ubiquitination and subsequent degradation by the proteasome. ML372 increased SMN protein levels in muscle, spinal cord, and brain tissue of SMA mice. Importantly, ML372 treatment improved the righting reflex and extended survival of a severe mouse model of SMA. These results demonstrate that slowing SMN degradation by selectively inhibiting its ubiquitination can improve the motor phenotype and lifespan of SMA model mice.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.