A5007778912- Muscle Physiology and Disorders
- Children's Physical and Motor Development
- Neurogenetic and Muscular Disorders Research
- Genetics and Neurodevelopmental Disorders
- Muscle activation and electromyography studies
- Genetic Neurodegenerative Diseases
- Cardiomyopathy and Myosin Studies
- Cerebral Palsy and Movement Disorders
- Virus-based gene therapy research
- Extracellular vesicles in disease
- Adipose Tissue and Metabolism
- Exercise and Physiological Responses
- Biotin and Related Studies
- Advanced Sensor and Energy Harvesting Materials
- Transcranial Magnetic Stimulation Studies
- Congenital heart defects research
- MicroRNA in disease regulation
- CRISPR and Genetic Engineering
- Muscle metabolism and nutrition
- Prosthetics and Rehabilitation Robotics
- Telomeres, Telomerase, and Senescence
- Mitochondrial Function and Pathology
- Nuclear Structure and Function
- Diet and metabolism studies
- Tissue Engineering and Regenerative Medicine
Great Ormond Street Hospital
2016-2025
University College London
2016-2025
NIHR Great Ormond Street Hospital Biomedical Research Centre
2019-2025
Great Ormond Street Hospital for Children NHS Foundation Trust
2012-2025
Solidus Biosciences (United States)
2017-2022
National Institute for Health Research
2020-2022
Leiden University Medical Center
2022
ORCID
2021
Ghent University Hospital
2015
Ghent University
2015
Aim Duchenne muscular dystrophy ( DMD ) is associated with neuropsychiatric disorders. The aim of the study was to characterize profile fully and explore underlying genotype/phenotype associations. Method One hundred thirty males (mean age 9y 10mo, range 5–17y) in four European centres were included completed IQ assessment a neurodevelopmental‐screening questionnaire. Of these, 87 underwent comprehensive using structured diagnostic interview parent‐reported questionnaires. Results overall...
To assess the current use of glucocorticoids (GCs) in Duchenne muscular dystrophy UK, and compare benefits adverse events daily versus intermittent prednisolone regimens.A prospective longitudinal observational study across 17 neuromuscular centres UK 360 boys aged 3-15 years with confirmed who were treated or (10 days on/10 off) for a mean duration treatment 4 years.The median loss ambulation was 12 14.5 treatment; HR 1.57 (95% CI 0.87 to 2.82). A fitted multilevel model comparing regiments...
Artificial intelligence has the potential to revolutionize healthcare, yet clinical trials in neurological diseases continue rely on subjective, semiquantitative and motivation-dependent endpoints for drug development. To overcome this limitation, we collected a digital readout of whole-body movement behavior patients with Duchenne muscular dystrophy (DMD) (n = 21) age-matched controls 17). Movement was assessed while participant engaged everyday activities using 17-sensor bodysuit during...
Abstract Friedreichʼs ataxia (FA) is caused by a variant of the Frataxin ( FXN ) gene, leading to its downregulation and progressively impaired cardiac neurological function. Current gold-standard clinical scales use simplistic behavioral assessments, which require 18- 24-month-long trials determine if therapies are beneficial. Here we captured full-body movement kinematics from patients with wearable sensors, enabling us define digital features based on data nine FA (six females three...
To investigate the associations between mutations expected to differentially affect Dp140 expression and long-term trajectories of respiratory upper-limb motor outcomes in Duchenne muscular dystrophy (DMD). In a retrospective analysis population-based longitudinal data from three real-world natural history sources, individuals with DMD aged 5 years 18 were subdivided according predicted effects participants' mutation on dystrophin isoform (group 1, Dp427 absent, Dp140/Dp71 present; group 2,...
<h3>Objective</h3> With the emergence of experimental therapies for Duchenne muscular dystrophy (DMD), it is fundamental to understand natural history this disorder properly design clinical trials. The aims study were assess effects produced on motor function by different <i>DMD</i> genotypes and early initiation glucocorticoids. <h3>Methods</h3> Through NorthStar Network, standardised data including Ambulatory Assessment score (NSAA) 513 ambulant UK boys with DMD analysed from 2004 2012....
The aim of this international collaborative effort was to report 36-month longitudinal changes using the 6MWT in ambulant patients affected by Duchenne muscular dystrophy amenable skip exons 44, 45, 51 or 53.
Duchenne muscular dystrophy (DMD) is caused by DMD mutations leading to dystrophin loss. Full-length Dp427 the primary isoform expressed in muscle and also central nervous system (CNS). Two shorter isoforms, Dp140 Dp71, are highly CNS. While a role for Dp71 on CNS comorbidities well known, relationships between expected disrupt motor outcomes not.Functional outcome data from 387 boys aged 4-15 years were subdivided mutation effects expression; Group 1 (Dp427 absent, Dp140/Dp71 present, n =...
In Duchenne muscular dystrophy (DMD), the reading frame of an out-of-frame DMD deletion can be repaired by antisense oligonucleotide (AO)-mediated exon skipping. This creates a shorter dystrophin protein, similar to those expressed in milder Becker (BMD). The skipping some exons may more efficacious than others. Patients with 44 or 45 skippable deletions (AOs clinical development) have less predictable phenotype for 51, group advanced trials. A way predict potential AOs is study patients BMD...
A number of promising experimental therapies for Duchenne muscular dystrophy (DMD) are emerging. Clinical trials currently rely on invasive biopsies or motivation-dependent functional tests to assess outcome. Quantitative muscle magnetic resonance imaging (MRI) could offer a valuable alternative and permit inclusion non-ambulant DMD subjects. The aims our study were explore the responsiveness upper-limb MRI muscle-fat measurement as non-invasive objective endpoint clinical in DMD,...
Purpose SMT C1100 is a utrophin modulator being evaluated as treatment for Duchenne muscular dystrophy (DMD). This study, the first in pediatric DMD patients, reports safety, tolerability and PK parameters of single multiple doses C1100, well analyze potential biomarkers muscle damage. Methods multicenter, Phase 1 study enrolled 12 divided equally into three groups (A–C). Group A were given 50 mg/kg on Days 11, bid 2 to 10. B C received 100 11; tid, respectively, safety review was performed...
The advent of therapeutic approaches for Duchenne muscular dystrophy (DMD) has highlighted the need to identify reliable outcome measures young boys with DMD. aim this study was develop a revised version North Star Ambulatory Assessment (NSAA) suitable between age 3 and 5 years by identifying appropriate items revising scoring system accordingly. Using scale in 171 controls 2.9 4.8 years, we identified that were at different points. An item defined as if it completed, achieving full score,...
The North Star ambulatory assessment (NSAA) is a functional motor outcome measure in Duchenne muscular dystrophy (DMD), widely used clinical trials and natural history studies, as well practice. However, little has been reported on the minimal clinically important difference (MCID) of NSAA. lack established MCID estimates for NSAA presents challenges interpreting significance results this trials, studies Combining statistical approaches patient perspectives, study estimated using...
Abstract Background Multiple clinical trials to assess the efficacy of AAV-directed gene transfer in participants with Duchenne muscular dystrophy (DMD) are ongoing. The success these currently relies on standard functional outcome measures that may exhibit variability within and between participants, rendering their use as sole drug challenging. Given this, supportive objective biomarkers be useful enhancing observed results. Creatine kinase (CK) is traditionally used a diagnostic biomarker...
Objectives Duchenne muscular dystrophy (DMD) is a rare neuromuscular disorder that causes progressive weakness and early death. Gene therapy an area of new therapeutic development. This qualitative study explored factors influencing parents' adult patients' preferences about gene therapy. Methods We report data from 17 parents children with DMD 6 patients. Participants responded to hypothetical vignette features including non-curative stabilizing benefits muscle, cardiac pulmonary function;...