ArticleOrphanet journal of rare diseases2014
Therapeutic strategies based on modified U1 snRNAs and chaperones for Sanfilippo C splicing mutations.
Article in Orphanet journal of rare diseases, 2014. 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, 45 citations in OpenAlex.
- Evaluation of GlcNAc-Configured Glycomimetics as Pharmacological Chaperones of NAGLU for the Treatment of Mucopolysaccharidosis IIIB.Biomolecules · 2026Article
- Rescue of common and rare exon 2 skipping variants of the GAA gene using modified U1 snRNA.Molecular medicine (Cambridge, Mass.) · 2025Article
- Current Concepts in the Management of Sanfilippo Syndrome (MPS III): A Narrative Review.Cureus · 2024Review
- Identification and characterization of novel genetic variants in the first Chinese family of mucopolysaccharidosis IIIC (Sanfilippo C syndrome).Journal of cellular and molecular medicine · 2024Article
- Mucopolysaccharidosis type IIIB: a current review and exploration of the AAV therapy landscape.Neural regeneration research · 2024Review
- Characterization and Engineered U1 snRNA Rescue of Splicing Variants in a Turkish Neurodevelopmental Disease Cohort.Human mutation · 2024Article
- Development of Engineered-U1 snRNA Therapies: Current Status.International journal of molecular sciences · 2023Review
- Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine.NPJ genomic medicine · 2023Review
- Article
- Engineered U1 snRNAs to modulate alternatively spliced exons.Methods (San Diego, Calif.) · 2022Article
- Glucosamine amends CNS pathology in mucopolysaccharidosis IIIC mouse expressing misfolded HGSNAT.The Journal of experimental medicine · 2022Article
- Splicing Modulation as a Promising Therapeutic Strategy for Lysosomal Storage Disorders: The Mucopolysaccharidoses Example.Life (Basel, Switzerland) · 2022Review
- How to Design U1 snRNA Molecules for Splicing Rescue.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Novel therapies for mucopolysaccharidosis type III.Journal of inherited metabolic disease · 2021Review
- Integrated Genome and Transcriptome Sequencing to Solve a Neuromuscular Puzzle: Miyoshi Muscular Dystrophy and Early Onset Primary Dystonia in Siblings of the Same Family.Frontiers in genetics · 2021Article
- Sanfilippo Syndrome: Molecular Basis, Disease Models and Therapeutic Approaches.International journal of molecular sciences · 2020Review
- Review
- Lysosomal Storage Disease-Associated Neuropathy: Targeting Stable Nucleic Acid Lipid Particle (SNALP)-Formulated siRNAs to the Brain as a Therapeutic Approach.International journal of molecular sciences · 2020Review
- A Compensatory U1snRNA Partially Rescues FAH Splicing and Protein Expression in a Splicing-Defective Mouse Model of Tyrosinemia Type I.International journal of molecular sciences · 2020Article
- A Cure for Sanfilippo Syndrome? A Summary of Current Therapeutic Approaches and their Promise.Medical research archives · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMutations affecting RNA splicing represent more than 20% of the mutant alleles in Sanfilippo syndrome type C, a rare lysosomal storage disorder that causes severe neurodegeneration. Many of these mutations are localized in the conserved donor or acceptor splice sites, while few are found in the nearby nucleotides.
methodsIn this study we tested several therapeutic approaches specifically designed for different splicing mutations depending on how the mutations affect mRNA processing. For three mutations that affect the donor site (c.234 + 1G > A, c.633 + 1G > A and c.1542 + 4dupA), different modified U1 snRNAs recognizing the mutated donor sites, have been developed in an attempt to rescue the normal splicing process. For another mutation that affects an acceptor splice site (c.372-2A > G) and gives rise to a protein lacking four amino acids, a competitive inhibitor of the HGSNAT protein, glucosamine, was tested as a pharmacological chaperone to correct the aberrant folding and to restore the normal trafficking of the protein to the lysosome.
resultsPartial correction of c.234 + 1G > A mutation was achieved with a modified U1 snRNA that completely matches the splice donor site suggesting that these molecules may have a therapeutic potential for some splicing mutations. Furthermore, the importance of the splice site sequence context is highlighted as a key factor in the success of this type of therapy. Additionally, glucosamine treatment resulted in an increase in the enzymatic activity, indicating a partial recovery of the correct folding.
conclusionsWe have assayed two therapeutic strategies for different splicing mutations with promising results for the future applications.
Indexed as
Identifiers
What OpenQuestion holds
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.