A5033643112- Muscle Physiology and Disorders
- RNA Research and Splicing
- Neurogenetic and Muscular Disorders Research
- RNA Interference and Gene Delivery
- Adipose Tissue and Metabolism
- CRISPR and Genetic Engineering
- Cardiomyopathy and Myosin Studies
- Virus-based gene therapy research
- RNA modifications and cancer
- Telomeres, Telomerase, and Senescence
- Genetic Neurodegenerative Diseases
- Tissue Engineering and Regenerative Medicine
- Biotin and Related Studies
- Viral Infections and Immunology Research
- Pluripotent Stem Cells Research
- RNA and protein synthesis mechanisms
- Genomics and Rare Diseases
- Muscle metabolism and nutrition
- Advanced biosensing and bioanalysis techniques
- Muscle activation and electromyography studies
- GDF15 and Related Biomarkers
- Advanced Sensor and Energy Harvesting Materials
- Silk-based biomaterials and applications
- Exercise and Physiological Responses
- RNA regulation and disease
Leiden University Medical Center
2016-2025
Leiden University
2006-2023
Great Ormond Street Hospital
2023
Analysis Group (United States)
2023
University College London
2023
Duchenne Parent Project
2023
Collaborative Group (United States)
2022
Newcastle University
2014-2020
Centre for Life
2014-2020
Muscular Dystrophy UK
2015-2020
Duchenne's muscular dystrophy is associated with severe, progressive muscle weakness and typically leads to death between the ages of 20 35 years. By inducing specific exon skipping during messenger RNA (mRNA) splicing, antisense compounds were recently shown correct open reading frame DMD gene thus restore dystrophin expression in vitro animal models vivo. We explored safety, adverse-event profile, local dystrophin-restoring effect a single, intramuscular dose an oligonucleotide, PRO051,...
Local intramuscular administration of the antisense oligonucleotide PRO051 in patients with Duchenne's muscular dystrophy relevant mutations was previously reported to induce skipping exon 51 during pre-messenger RNA splicing dystrophin gene and facilitate new expression muscle-fiber membranes. The present phase 1-2a study aimed assess safety, pharmacokinetics, molecular clinical effects systemically administered PRO051.We weekly abdominal subcutaneous injections for 5 weeks 12 patients,...
Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, improved clinical care. Locus-specific databases allow collection, organization, storage, analysis genetic variants disease. Here, we describe development TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed data 7,149 held within database. A total 5,682 large were observed (80%...
With the Food and Drug Administration (FDA) approval of nusinersen (tradename Spinraza) for treatment spinal muscular atrophy patients on December 23 [1], 2016 brought us not one, but two approved splice modulating oligonucleotides to treat neuromuscular disorders.Eteplirsen, an oligonucleotide a subset Duchenne dystrophy (DMD) patients, was earlier this year.However, where eteplirsen highly controversial [2], one seemed be crystal clear: drug only 91 days after Bioeen filed new application...
Abstract Antisense oligonucleotides (ASOs) are incredibly versatile molecules that can be designed to specifically target and modify RNA transcripts slow down or halt rare genetic disease progression. They offer the potential groups of patients tailored for individual cases. Nonetheless, not all variants disorders amenable ASO-based treatments, hence, it is important consider several factors before embarking on drug development journey. Here, we discuss which have benefit from a specific...
The dystrophin deficiency leading to the severely progressing muscle degeneration in Duchenne muscular dystrophy (DMD) patients is caused by frame-shifting mutations DMD gene. We are developing a reading frame correction therapy aimed at antisense-induced skipping of targeted exons from pre-mRNA. Despite introducing (larger) deletion, an in-frame transcript generated that allows synthesis slightly shorter, but largely functional as found mostly milder Becker (BMD). have recently demonstrated...
Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting disorder for which no cure available. Nevertheless, several potential pharmaceutical compounds gene therapy approaches have progressed into clinical trials. With improvement in function being the most important end point these trials, lot of emphasis has been placed on setting up reliable, reproducible, easy to perform functional tests pre clinically assess function, strength, condition, coordination mdx mouse model...
Abstract Background Antisense‐mediated exon skipping is a putative treatment for Duchenne muscular dystrophy (DMD). Using antisense oligonucleotides (AONs), the disrupted DMD reading frame restored, allowing generation of partially functional dystrophin and conversion severe into milder Becker phenotype. In vivo studies are mainly performed using 2′‐ O ‐methyl phosphorothioate (2OMePS) or morpholino (PMO) AONs. These compounds were never directly compared. Methods mdx humanized (h)DMD mice...
Phage display screenings are frequently employed to identify high-affinity peptides or antibodies. Although successful, phage is a laborious technology and notorious for identification of false positive hits. To accelerate improve the selection process, we have Illumina next generation sequencing deeply characterize Ph.D.-7 M13 peptide library before after several rounds biopanning on KS483 osteoblast cells. Sequencing naive one round amplification in bacteria identifies propagation...
Abstract Duchenne muscular dystrophy (DMD) is a with high incidence of learning and behavioural problems associated neurodevelopmental disorders. To gain more insights into the role dystrophin in this cognitive phenotype, we performed comprehensive analysis expression patterns isoforms across human brain development, using unique transcriptomic data from Allen Human Brain BrainSpan atlases. Dystrophin show large changes through life pronounced differences between foetal adult brain. The...