Ascorbic acid for the treatment of Charcot-Marie-Tooth disease

Gess, Burkhard; Baets, Jonathan; Jonghe, Peter De; Reilly, Mary M.; Pareyson, Davide; Young, Peter

doi:10.1002/14651858.cd011952

Cited by 43 publications

(39 citation statements)

References 61 publications

(14 reference statements)

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“…Initial efforts to treat CMT1A have focused on strategies that reduce PMP22 expression such as with vitamin C and progesterone antagonists. Unfortunately, these treatments have either been unsuitable for clinical trials (progesterone antagonists) or ineffective in clinical trials (vitamin C) [21,22]. A study of eight CMT1A patients demonstrated a mild positive effect of neurotrophin-3 (NT-3) on the sensory and reflex scores of the neuropathy impairment score [23], an effect replicated in a mouse model of CMT1A in which there was adeno-associated virus-mediated muscle overexpression of NT-3 [24].…”

Section: Therapeutic Advances In Cmt1mentioning

confidence: 99%

Recent advances in the genetic neuropathies

Rossor

Tomaselli

Reilly

2016

Current Opinion in Neurology

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Purpose of review Charcot-Marie-Tooth disease (CMT) is one of the commonest inherited neuromuscular diseases with a population prevalence of 1 in 2500. This review will cover recent advances in the genetics and pathomechanisms of CMT and how these are leading to the development of rational therapies. Recent findings Pathomechanistic and therapeutic target advances in CMT include the identification of the ErbB receptor signalling pathway as a therapeutic target in CMT1A and pharmacological modification of the unfolded protein response in CMT1B. In CMT2D, due to mutations in GARS, VEGF-mediated stimulation of the Nrp1 receptor has been identified as a therapeutic target. Preclinical advances have been accompanied by the publication of large natural history cohorts and the identification of a sensitive biomarker of disease (muscle MRI) that is able to detect disease progression in CMT1A over one year. Summary Advances in next generation sequencing technology, cell biology and animal models of CMT are paving the way for rational treatments. The combination of robust natural history data and the identification of sensitive biomarkers mean that we are now entering an exciting therapeutic era in the field of the genetic neuropathies.

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Section: Therapeutic Advances In Cmt1mentioning

confidence: 99%

Recent advances in the genetic neuropathies

Rossor

Tomaselli

Reilly

2016

Current Opinion in Neurology

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“…discovered that in vitro ascorbic acid suppresses PMP22 expression via reducing cAMP and adenylate cyclase activity (Kaya et al, 2007), in several double-blind clinical trials ascorbic acid was ineffective in ameliorating disease phenotypes (Burns et al, 2009; Lewis et al, 2013; Micallef et al, 2009; Pareyson et al, 2011; Verhamme et al, 2009). Potential explanations for the discrepancies between the animal and human studies include the outcome parameters used in the human studies, as well as the duration of the treatment regimen (Gess et al, 2015). It is possible that longer studies and more sensitive outcome measures would reveal benefits of ascorbate on neuropathy progression.…”

Section: Small Molecule Therapiesmentioning

confidence: 99%

Promoting peripheral myelin repair

Zhou

Notterpek

2016

Experimental Neurology

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Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the target of myelin repair strategies in acute injuries and chronic diseases, such as hereditary demyelinating neuropathies. In one approach, the endogenous regenerative capacity of Schwann cells is enhanced through interventions such as exercise, electrical stimulation or pharmacological means. Alternatively, Schwann cells derived from healthy nerves, or engineered from different tissue sources have been transplanted into the PNS to support remyelination. These transplant approaches can then be further enhanced by exercise and/or electrical stimulation, as well as by the inclusion of biomaterial engineered to support glial cell viability and neurite extension. Advances in our basic understanding of peripheral nerve biology, as well as biomaterial engineering, will further improve the functional repair of myelinated peripheral nerves.

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“…Currently, there are no approved treatments for CMT1A disease though there have been considerable interest in the potential of ascorbic acid (AA) as a therapy leading to six clinical trials investigating the efficacy of AA on CMT1A [6–11]. Unfortunately, no beneficial clinical effects of AA were identified in any of these trials, as confirmed by two meta-analyses [12,13]. Recently, a clinical trial of PXT3003 (a fixed combination of baclofen, naltrexone and sorbitol) showed preliminary evidence of efficacy in an exploratory phase 2 study [14], which was also confirmed by a meta-analysis [12].…”

Section: Introductionmentioning

confidence: 99%

A Rasch Analysis of the Charcot-Marie-Tooth Neuropathy Score (CMTNS) in a Cohort of Charcot-Marie-Tooth Type 1A Patients

et al. 2017

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The Charcot-Marie-Tooth Neuropathy Score (CMTNS) was developed as a main efficacy endpoint for application in clinical trials of Charcot-Marie-Tooth disease type 1A (CMT1A). However, the sensitivity of the CMTNS for measuring disease severity and progression in CMT1A patients has been questioned. Here, we applied a Rasch analysis in a French cohort of patients to evaluate the psychometrical properties of the CMTNS. Overall, our analysis supports the validity of the CMTNS for application to CMT1A patients though with some limitations such as certain items of the CMTNS being more suitable for moderate to severe forms of the disease, and some items being disordered. We suggest that additional items and/or categories be considered to better assess mild-to-moderate patients.

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Ascorbic acid for the treatment of Charcot-Marie-Tooth disease

Cited by 43 publications

References 61 publications

Recent advances in the genetic neuropathies

Recent advances in the genetic neuropathies

Promoting peripheral myelin repair

A Rasch Analysis of the Charcot-Marie-Tooth Neuropathy Score (CMTNS) in a Cohort of Charcot-Marie-Tooth Type 1A Patients

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