A5014300635- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Neurological disorders and treatments
- Innovations in Medical Education
- Tryptophan and brain disorders
- Amyotrophic Lateral Sclerosis Research
- Parkinson's Disease Mechanisms and Treatments
- Diversity and Career in Medicine
- Health and Medical Research Impacts
- Hereditary Neurological Disorders
- Healthcare Quality and Management
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Systemic Sclerosis and Related Diseases
- Calcium signaling and nucleotide metabolism
- PARP inhibition in cancer therapy
- COVID-19 and healthcare impacts
- Global Health Workforce Issues
- Primary Care and Health Outcomes
- Advanced Neuroimaging Techniques and Applications
- Botulinum Toxin and Related Neurological Disorders
- Medical Imaging Techniques and Applications
- Neurological diseases and metabolism
- RNA Research and Splicing
- Animal testing and alternatives
Huntington's Disease Association
2016-2024
University College London
2016-2024
National Hospital for Neurology and Neurosurgery
2016-2024
Beaumont Hospital
2024
General Medical Council
2024
UK Dementia Research Institute
2018-2023
Thomas Foundation
2022
Guy's and St Thomas' NHS Foundation Trust
2022
University of California, Los Angeles
2022
Accreditation Council for Graduate Medical Education
2010-2021
BackgroundBlood biomarkers of neuronal damage could facilitate clinical management and therapeutic development for Huntington's disease. We investigated whether neurofilament light protein NfL (also known as NF-L) in blood is a potential prognostic marker neurodegeneration patients with disease.MethodsWe did retrospective analysis healthy controls carriers CAG expansion mutations HTT participating the 3-year international TRACK-HD study. studied associations between concentrations plasma MRI...
Highlights•Oligodendrocytes, not Schwann cells, form myelin sheaths without axonal signals•Oligodendrocytes sense diameter, increasing sheath length with larger fibers•Oligodendrocytes from cortex and spinal cord of different lengths•Regional differences in lengths may initially be hard-wiredSummarySince Río-Hortega's description oligodendrocyte morphologies nearly a century ago, many studies have observed sheath-length diversity between CNS regions [1–3]. Myelin directly impacts conduction...
Huntington's disease (HD) is a genetic progressive neurodegenerative disorder, caused by mutation in the HTT gene, for which there currently no cure. The identification of sensitive indicators progression and therapeutic outcome could help development effective strategies treating HD. We assessed mutant huntingtin (mHTT) neurofilament light (NfL) protein concentrations cerebrospinal fluid (CSF) blood parallel with clinical evaluation magnetic resonance imaging premanifest manifest HD...
Disease-modifying treatments are in development for Huntington's disease; crucial to their success is identify a timepoint patient's life when there measurable biomarker of early neurodegeneration while clinical function still intact. We aimed this novel cohort young adult premanifest disease gene carriers (preHD) far from predicted symptom onset.
Longitudinal analysis in 80 patients shows that mutant huntingtin and neurofilament light could predict Huntington’s disease progression.
Chronic cellular stress associated with neurodegenerative disease can result in the persistence of granule (SG) structures, membraneless organelles that form response to stress. In Huntington's (HD), chronic expression mutant huntingtin generates various forms stress, including activation unfolded protein and oxidative However, it has yet be determined whether SGs are a feature HD neuropathology. We examined miRNA composition extracellular vesicles (EVs) present cerebrospinal fluid (CSF)...
Abstract Neurofilament light chain is an established marker of neuroaxonal injury that elevated in CSF and blood across various neurological diseases. It increasingly used clinical practice to aid diagnosis monitor progression as outcome measure assess safety efficacy disease-modifying therapies the translational neuroscience field. Quantitative methods for neurofilament human biofluids have relied on immunoassays, which limited capacity describe structure protein how this might vary...
Neurofilament light (NfL) protein in blood plasma has been proposed as a prognostic biomarker of neurodegeneration number conditions, including Huntington disease (HD). This study investigates the regional distribution NfL-associated neural pathology HD gene expansion carriers.
Huntington's disease (HD) is a hereditary neurodegenerative condition with no therapeutic intervention known to alter progression, but several trials are ongoing and biomarkers of progression needed. Tau an axonal protein, often altered in neurodegeneration, recent studies pointed out its role on HD neuropathology. Our goal was study whether cerebrospinal fluid (CSF) tau biomarker HD. After informed consent, healthy controls, pre-symptomatic symptomatic gene expansion carriers were recruited...
Immune system activation is involved in Huntington's disease (HD) pathogenesis and biomarkers for this process could be relevant to study the characterise therapeutic response specific interventions. We aimed inflammatory cytokines microglial markers CSF of HD patients.
A significant proportion of elderly and psychiatric patients do not have the capacity to make health care decisions. We suggest that machine learning technologies could be harnessed integrate data mined from electronic records (EHRs) social media in order estimate confidence prediction a patient would consent given treatment. call this process
Huntington disease (HD) is a neurodegenerative caused by CAG trinucleotide repeat expansion in the huntingtin ( HTT ) gene. Therapeutics that lower have shown preclinical promise and are being evaluated clinical trials. However, assessment of brain lowering presents challenges. We reported mutant (mHTT) CSF HD patients correlates with measures, including burden as well motor cognitive performance. also brains mice results correlative reduction mHTT CSF, prompting use this measure an...
Alzheimer's disease (AD) is characterized by the intra- and extracellular accumulation of amyloid-β (Aβ) peptides. How Aβ aggregates perturb proteome in brains patients AD transgenic mouse models, remains largely unclear. State-of-the-art mass spectrometry (MS) methods can comprehensively detect proteomic alterations, providing relevant insights unobtainable with transcriptomics investigations. Analyses relationship between progressive aggregation protein abundance changes 5xFAD mice have...
Background: The measurement of disease-relevant biomarkers has become a major component clinical trial design, but in the absence rigorous and analytical validation detection methodology, interpretation results may be misleading.In Huntington's disease (HD), concentration mutant huntingtin protein (mHTT) cerebrospinal fluid (CSF) patients serve as both progression biomarker pharmacodynamic readout for HTT-lowering therapeutic approaches.We recently published quantification mHTT levels HD...
Background Remote monitoring of Huntington disease (HD) signs and symptoms using digital technologies may enhance early clinical diagnosis tracking progression, guide treatment decisions, monitor response to disease-modifying agents. Several recent studies in neurodegenerative diseases have demonstrated the feasibility symptom monitoring. Objective The aim this study was evaluate a novel smartwatch- smartphone-based platform remotely HD. Methods This analysis aimed determine reliability...
Abstract Converging lines of evidence from several models, and post‐mortem human brain tissue studies, support the involvement kynurenine pathway (KP) in Huntington's disease (HD) pathogenesis. Quantifying KP metabolites HD biofluids is desirable, both to study pathobiology as a potential source biomarkers quantify dysfunction evaluate biochemical impact therapeutic interventions targeting its components. In prospective single‐site controlled cohort with standardised collection cerebrospinal...
Huntington disease (HD) is a genetic neurodegenerative caused by cytosine, adenine, guanine (CAG) expansion in the
Biomarkers of Huntington's disease (HD) in cerebrospinal fluid (CSF) could be value elucidating the biology this genetic neurodegenerative disease, as well development novel therapeutics. Deranged synaptic and immune function have been reported HD, concentrations protein neurogranin microglial TREM2 are increased other diseases. We therefore used ELISAs to quantify CSF samples from HD mutation carriers controls. concentration was not significantly altered compared controls, nor it associated...
Investigating early white matter (WM) change in Huntington's disease (HD) can improve our understanding of the way which spreads from striatum.
Abstract Brain-derived neurotrophic factor (BDNF) is implicated in the survival of striatal neurons. BDNF function reduced Huntington’s disease (HD), possibly because mutant huntingtin impairs its cortico-striatal transport, contributing to neurodegeneration. The trophic pathway a therapeutic target, and blood has been suggested as potential biomarker for HD, but not quantified cerebrospinal fluid (CSF) HD. We CSF plasma HD-CSF cohort (20 pre-manifest 40 manifest HD mutation carriers 20 age...
Abstract Background Juvenile‐onset Huntington's disease (JOHD) is a rare and particularly devastating form of (HD) for which clinical diagnosis challenging robust outcome measures are lacking. Neurofilament light protein (NfL) in plasma has emerged as prognostic biomarker adult‐onset HD. Methods We performed retrospective analysis samples data collected between 2009 2020 from the Kids‐HD Kids‐JHD studies. Plasma children young adults with JOHD, premanifest HD (preHD) mutation carriers,...