Pamela J. Shaw
A5087727224- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Parkinson's Disease Mechanisms and Treatments
- Neurological diseases and metabolism
- Genetic Neurodegenerative Diseases
- Alzheimer's disease research and treatments
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Hereditary Neurological Disorders
- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Ion channel regulation and function
- Prion Diseases and Protein Misfolding
- biodegradable polymer synthesis and properties
- Cancer-related gene regulation
- RNA regulation and disease
- Muscle Physiology and Disorders
- Botulinum Toxin and Related Neurological Disorders
- Dysphagia Assessment and Management
- Nerve injury and regeneration
- Lung Cancer Diagnosis and Treatment
- Cardiac, Anesthesia and Surgical Outcomes
- Parkinson's Disease and Spinal Disorders
- Biochemical Acid Research Studies
University of Sheffield
2016-2025
Sheffield Teaching Hospitals NHS Foundation Trust
2016-2025
Emory University
2009-2025
King's College London
2012-2024
Royal Hallamshire Hospital
2008-2024
Cedars-Sinai Medical Center
2018-2024
Novartis (United States)
2024
Neuroscience Institute
2024
King's College - North Carolina
2024
Royal Free London NHS Foundation Trust
2023
We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with large proportion cases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).We screened 4448 patients diagnosed ALS (El Escorial criteria) 1425 FTD (Lund-Manchester from 17 regions worldwide for GGGGCC using repeat-primed PCR assay. assessed familial disease status on basis self-reported family history similar neurodegenerative diseases at time sample...
Abstract Objective Amyotrophic lateral sclerosis (ALS) is a common, fatal motor neuron disorder with no effective treatment. Approximately 10% of cases are familial ALS (FALS), and the most common genetic abnormality superoxide dismutase ‐ 1 ( SOD1 ) mutations. Most research in past decade has focused on neurotoxicity mutant SOD1, this knowledge directed therapeutic strategies. We recently identified TDP‐43 as major pathological protein sporadic ALS. In study, we investigated larger series...
Background and Purpose— “Incidental” MRI white matter (WM) lesions, comprising periventricular lesions (PVLs) deep subcortical (DSCLs), are common in the aging brain. Direct evidence of ischemia associated with incidental WM (WMLs) has been lacking, their pathogenesis is unresolved. Methods— A population-based, postmortem cohort (n=456) donated brains was examined by pathology. In a subsample whole cohort, magnetic resonance images were used to sample compare WMLs nonlesional for molecular...
The intrathecally administered antisense oligonucleotide tofersen reduces synthesis of the superoxide dismutase 1 (SOD1) protein and is being studied in patients with amyotrophic lateral sclerosis (ALS) associated mutations SOD1 (SOD1 ALS).
As part of a prospective study the neurologic and neuropsychological complications coronary artery bypass graft surgery, 312 patients were compared with control group 50 undergoing major surgery for peripheral vascular disease. The purpose comparing 2 groups was to determine what extent after heart can be attributed cardiopulmonary bypass. similar respect age, preoperative intellectual status, anesthetic methods, duration operation, perioperative complications, time spent in intensive...
Objective An intronic GGGGCC-repeat expansion of C9ORF72 is the most common genetic variant amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. The mechanism neurodegeneration unknown, but a direct effect on RNA processing mediated by foci transcribed from repeat sequence has been proposed. Methods Gene expression profiling utilised total extracted motor neurons lymphoblastoid cell lines derived human ALS patients, including those with an C9ORF72, controls. In lines, length...
Tofersen is an antisense oligonucleotide that mediates the degradation of superoxide dismutase 1 (SOD1) messenger RNA to reduce SOD1 protein synthesis. Intrathecal administration tofersen being studied for treatment amyotrophic lateral sclerosis (ALS) due mutations.We conducted a phase 1-2 ascending-dose trial evaluating in adults with ALS mutations. In each dose cohort (20, 40, 60, or 100 mg), participants were randomly assigned 3:1 ratio receive five doses placebo, administered...
Amyotrophic lateral sclerosis (ALS) is a late-onset neurological disorder characterized by death of motoneurons. Mutations in Cu/Zn superoxide dismutase-1 (SOD1) cause familial ALS but the mechanisms whereby they induce disease are not fully understood. Here, we use time-lapse microscopy to monitor for first time effect mutant SOD1 on fast axonal transport (FAT) bona fide cargoes living neurons. We analyzed FAT mitochondria that known target damage and also membrane-bound organelles (MBOs)...
Mutation in the CHMP2B gene has been implicated frontotemporal dementia. The authors screened patients with ALS and several cohorts of control samples. They identified mutations (Q206H; I29V) two non-SOD1 ALS. Neuropathology Q206H case showed lower motor neuron predominant disease ubiquitylated inclusions neurons. Antibodies to p62 (sequestosome 1) novel oligodendroglial cortex.
A GGGGCC hexanucleotide repeat expansion in the C9orf72 gene is most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). encodes two protein isoforms unclear function. Reduced levels expression have been reported C9ALS/FTD patients, although haploinsufficiency has proposed to contribute C9ALS/FTD, its significance not yet clear. Here, we report that interacts with Rab1a Unc-51-like kinase 1 (ULK1) autophagy initiation complex. As a effector,...
A prospective study of 312 patients undergoing elective coronary artery bypass surgery was undertaken to determine the incidence, severity, and functional impact postoperative neurological complications. Detailed evaluation showed that complications after were common, occurring in 191 (61%). Although such a high proportion total developed detectable changes, serious morbidity rare. Neurological disorders resulted death only one patient (0.3%) severe disability four (1.3%). Forty eight mildly...