ReviewDegenerative neurological and neuromuscular disease2019
The effects of huntingtin-lowering: what do we know so far?
Review in Degenerative neurological and neuromuscular disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 34 citations in OpenAlex.
- An orally available, brain penetrant, small molecule lowers huntingtin levels by enhancing pseudoexon inclusion.Nature communications · 2022Trial
- Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Development and Clinical Applications of Antisense Oligonucleotide Gapmers.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Rationally Engineered Small Molecules: Pharmacophore Modeling and Molecular Docking Studies Targeting Toxic Polyglutamine (PolyQ) Repeats in Huntington's Disease.Current drug targets · 2026Article
- Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.bioRxiv : the preprint server for biology · 2025Article
- Advances in gene and cellular therapeutic approaches for Huntington's disease.Protein & cell · 2025Review
- Technologies for Targeted RNA Degradation and Induced RNA Decay.Chemical reviews · 2024Review
- Preclinical evaluation of stereopure antisense oligonucleotides for allele-selective lowering of mutantMolecular therapy. Nucleic acids · 2024Article
- Global huntingtin knockout in adult mice leads to fatal neurodegeneration that spares the pancreas.Life science alliance · 2024Article
- Latest advances on new promising molecular-based therapeutic approaches for Huntington's disease.Journal of translational internal medicine · 2024Article
- Huntington's Disease: Complex Pathogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Mono- and Biallelic Inactivation of Huntingtin Gene in Patient-Specific Induced Pluripotent Stem Cells Reveal HTT Roles in Striatal Development and Neuronal Functions.Journal of Huntington's disease · 2024Article
- Cas9-mediated replacement of expanded CAG repeats in a pig model of Huntington's disease.Nature biomedical engineering · 2023Article
- Cyclodextrin-Based Nanoparticles for Delivery of Antisense Oligonucleotides Targeting Huntingtin.Pharmaceutics · 2023Article
- Article
- Delivering the Promise of Gene Therapy with Nanomedicines in Treating Central Nervous System Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Review
- Therapeutic Strategies in Huntington's Disease: From Genetic Defect to Gene Therapy.Biomedicines · 2022Review
- Current and Possible Future Therapeutic Options for Huntington's Disease.Journal of central nervous system disease · 2022Review
- Emerging Therapies for Huntington's Disease - Focus on N-Terminal Huntingtin and Huntingtin Exon 1.Biologics : targets & therapy · 2022Review
- Differential development and electrophysiological activity in cultured cortical neurons from the mouse and cynomolgus monkey.Neural regeneration research · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapies targeting mutant huntingtin DNA, mRNA, and protein have a chance at becoming the first disease-modifying treatments for Huntington's disease, a fatal inherited neurodegenerative disorder for which only symptom management treatments are available today. This review focuses on evidence addressing several key questions pertinent to huntingtin-lowering, ranging from the functions of wild-type huntingtin (wtHTT) that may be disrupted by huntingtin-lowering treatments through the various ways huntingtin can be lowered, the tolerability of wtHTT-lowering in mice and primates, what has been found in the Ionis Pharmaceutical safety trial of a huntingtin-lowering therapy, and to the question of how much mutant huntingtin may need to be lowered for a therapy to be clinically effective. We conclude that adverse consequences of lowering wtHTT in animals appear to be brain region-specific, and/or dependent upon the animal's stage of development and the amount by which huntingtin is lowered. Therefore, safe approaches to huntingtin-lowering in patients may be to lower huntingtin only moderately, or lower huntingtin only in the most affected brain regions, or lower huntingtin allele-selectively, or all of the above. Many additional questions about huntingtin-lowering remain open, and will only be answered by upcoming clinical trials, such as whether the delivery approaches currently planned will be adequate to get the treatment to the necessary brain regions, and whether non-allele-selective huntingtin-lowering will be safe in the long run. Meantime, there is a role for preclinical research to address key knowledge gaps, including the effects of non-allele-selective huntingtin-lowering on protein trafficking and viability at the cellular level, the tolerability of wtHTT-lowering in the corticostriatal connections of the primate brain, and the effects of this lowering on the functioning of neurotransmitter systems and the transport of neurotrophic factors to the striatum.
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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.