Trial reportNature communications2022
An orally available, brain penetrant, small molecule lowers huntingtin levels by enhancing pseudoexon inclusion.
Trial report in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02268552 (An Open Label Multi-part First-in-human Study of Oral LMI070 in Infants With Type 1 Spinal Muscular Atrophy), which is not on this map. Cited by 71 papers.
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.
An Open Label Multi-part First-in-human Study of Oral LMI070 in Infants With Type 1 Spinal Muscular Atrophy
Who cites it
71 citing papers in PubMed, 118 citations in OpenAlex.
- Oral splicing modulator branaplam in Huntington's disease: a phase 2 randomized controlled trial.Nature medicine · 2026Trial
- An alternative splicing modulator decreases mutant HTT and improves the molecular fingerprint in Huntington's disease patient neurons.Nature communications · 2022Trial
- The cellular landscape of druggable RNA-binding proteins.Nature reviews. Drug discovery · 2026Review
- The HTT1a protein initiates HTT aggregation in a knock-in mouse model of Huntington's disease.Brain : a journal of neurology · 2026Article
- Specificity and exon target space of splicing modifying compounds.Nature communications · 2026Article
- Anle138b ameliorates pathological phenotypes in mouse and cellular models of Huntington's disease.EMBO molecular medicine · 2026Article
- Depleting prion protein using splice-switching small molecules.bioRxiv : the preprint server for biology · 2026Article
- Tunable gene control via RNA splicing with a clinically approved small molecule.Nature communications · 2026Article
- Review
- SpliceHarmonization: an integrated method for identifying RNA splicing events in therapeutics for splicing modulation.Bioinformatics (Oxford, England) · 2026Article
- Article
- An orthogonal TRAP enables intersectional genetic access to activated neurons in the mouse brain.bioRxiv : the preprint server for biology · 2026Article
- Engineered Source-Specific Extracellular Vesicles for Neurodegenerative Diseases: From Biological Barriers to Targeted Delivery Strategies.International journal of nanomedicine · 2026Review
- Therapeutic strategies for spinal muscular atrophy: the history and future perspective.Frontiers in human neuroscience · 2026Review
- Chemically-inducible CRISPR/Cas9 circuits for ultra-high dynamic range gene perturbation.Nature communications · 2025Article
- Unbiased RNA Degrader Identification Uncovers an LC3B-Recruiting Chimera forJournal of the American Chemical Society · 2025Article
- Natural products proposed for the management of Huntington's disease (HD): a comprehensive review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Sequence-Independent RNA Sensing in Living Mammalian Cells.bioRxiv : the preprint server for biology · 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
- Mechanistic studies of small molecule ligands selective to RNA single G bulges.Nucleic acids research · 2025Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Huntington's Disease (HD) is a progressive neurodegenerative disorder caused by CAG trinucleotide repeat expansions in exon 1 of the huntingtin (HTT) gene. The mutant HTT (mHTT) protein causes neuronal dysfunction, causing progressive motor, cognitive and behavioral abnormalities. Current treatments for HD only alleviate symptoms, but cerebral spinal fluid (CSF) or central nervous system (CNS) delivery of antisense oligonucleotides (ASOs) or virus vectors expressing RNA-induced silencing (RNAi) moieties designed to induce mHTT mRNA lowering have progressed to clinical trials. Here, we present an alternative disease modifying therapy the orally available, brain penetrant small molecule branaplam. By promoting inclusion of a pseudoexon in the primary transcript, branaplam lowers mHTT protein levels in HD patient cells, in an HD mouse model and in blood samples from Spinal Muscular Atrophy (SMA) Type I patients dosed orally for SMA (NCT02268552). Our work paves the way for evaluating branaplam's utility as an HD therapy, leveraging small molecule splicing modulators to reduce expression of dominant disease genes by driving pseudoexon inclusion.
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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.