Common Pathophysiological Features of Charcot-Marie-Tooth Disease
type: CreativeWork
description: Hereditary peripheral neuropathy, also known as Charcot-Marie-Tooth disease (CMT) and related disorders, are a group of genetic disorders causing length-dependant neuropathy, resulting in motor and/or sensory loss progressing from the lower extremities toward the spine. With a population prevalence of 1 in 2,500, CMT is the most common inherited neuromuscular disorder and among the most common of all Mendelian diseases. Despite advances in the understanding of CMT genomics, a significant number of CMT patients remain genetically undiagnosed, and disease-modifying therapeutics are not available for the vast majority of CMT patients. In this thesis I present four topics addressing related areas of unmet need within the CMT field. My aim is to identify biological features relevant to a broad range of subtypes and experimental models, bridging the division between clinical and basic science. Firstly, I perform a systemic review of therapeutic studies of inherited peripheral neuropathies, with a focus specifically on gene and variant-level, rather than disease-level, treatment outcomes. Therapeutics for neuromuscular diseases are often gene- or mutation-specific, and I identify several variant-specific therapies and therapeutic approaches for inherited neuropathies, as well as variant-specific outcomes for gene-specific therapies, to be integrated into an online genetic diagnostic platform. Within the clinical trials I identify lack of responsive CMT biomarkers as a major limiting factor for therapeutic trials. Therefore, I next seek to identify novel biomarkers, by applying proteomics in a cohort of CMT patients and mouse models to identify neural cell adhesion molecular 1 (NCAM1) and growth differentiation factor 15 (GDF15) as serum biomarkers of CMT. NCAM1 may potentially function as a disease-progression biomarker, whereas GDF15 is indicated to be a very accurate diagnostic biomarker. Additionally, I find that broad elevation of serum complement proteins across CMT s…
abstract: Hereditary peripheral neuropathy, also known as Charcot-Marie-Tooth disease (CMT) and related disorders, are a group of genetic disorders causing length-dependant neuropathy, resulting in motor and/or sensory loss progressing from the lower extremities toward the spine. With a population prevalence of 1 in 2,500, CMT is the most common inherited neuromuscular disorder and among the most common of all Mendelian diseases. Despite advances in the understanding of CMT genomics, a significant number of CMT patients remain genetically undiagnosed, and disease-modifying therapeutics are not available for the vast majority of CMT patients. In this thesis I present four topics addressing related areas of unmet need within the CMT field. My aim is to identify biological features relevant to a broad range of subtypes and experimental models, bridging the division between clinical and basic science. Firstly, I perform a systemic review of therapeutic studies of inherited peripheral neuropathies, with a focus specifically on gene and variant-level, rather than disease-level, treatment outcomes. Therapeutics for neuromuscular diseases are often gene- or mutation-specific, and I identify several variant-specific therapies and therapeutic approaches for inherited neuropathies, as well as variant-specific outcomes for gene-specific therapies, to be integrated into an online genetic diagnostic platform. Within the clinical trials I identify lack of responsive CMT biomarkers as a major limiting factor for therapeutic trials. Therefore, I next seek to identify novel biomarkers, by applying proteomics in a cohort of CMT patients and mouse models to identify neural cell adhesion molecular 1 (NCAM1) and growth differentiation factor 15 (GDF15) as serum biomarkers of CMT. NCAM1 may potentially function as a disease-progression biomarker, whereas GDF15 is indicated to be a very accurate diagnostic biomarker. Additionally, I find that broad elevation of serum complement proteins across CMT s…
author: Jennings, Matthew James
language: eng
keywords: Charcot-Marie-Tooth, peripheral nerve, neuropathy, neurogenetic, neuromuscular, neuroscience, genetics, neurodegeneration, bioinformatics, biomarkers
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2022-11-01
date modified: 2026-07-22T22:23:56Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.83321