SUMMARY:
This article is protected by copyright. All rights reserved.
TITLE:
Charcot-Marie-Tooth neuropathies: current gene therapy advances and the route towards translation
DESCRIPTION:
Charcot-Marie-Tooth (CMT) neuropathies are a group of genetically and phenotypically heterogeneous disorders that predominantly affect the peripheral nervous system. Unravelling the genetic and molecular mechanisms, as well as the cellular effects of CMT mutations has facilitated the development of promising gene therapy approaches. Proposed gene therapy treatments for CMTs include virally or non-virally mediated gene replacement, addition, silencing, modification and editing of genetic…
CONTENT:
J Peripher Nerv Syst. 2023 Mar 25. doi: 10.1111/jns.12543. Online ahead of print.
ABSTRACT
Charcot-Marie-Tooth (CMT) neuropathies are a group of genetically and phenotypically heterogeneous disorders that predominantly affect the peripheral nervous system. Unravelling the genetic and molecular mechanisms, as well as the cellular effects of CMT mutations has facilitated the development of promising gene therapy approaches. Proposed gene therapy treatments for CMTs include virally or non-virally mediated gene replacement, addition, silencing, modification and editing of genetic material. For most CMT neuropathies gene- and disease- and even mutation- specific therapy approaches targeting the neuronal axon or myelinating Schwann cells may be needed, due to the diversity of underlying cellular and molecular-genetic mechanisms. The efficiency of gene therapies to improve the disease phenotype has been tested mostly in vitro and in in vivo rodent models that reproduce different molecular and pathological aspects of CMT neuropathies. In the next stage, bigger animal models, in particular non-human-primates, provide important insights into the translatability of the proposed administration and dosing, demonstrating scale-up potential and safety. The path towards clinical trials is faced with further challenges, but is becoming increasingly feasible owing to the progress and knowledge gained from clinical applications of gene therapies for other neurological disorders, as well as the emergence of sensitive outcome measures and biomarkers in patients with CMT neuropathies. This article is protected by copyright. All rights reserved.
PMID:36965137 | DOI:10.1111/jns.12543
SOURCE:
Journal of the peripheral nervous system : JPNS
TAGS:
This article is protected by copyright All rights reserved This article is protected by copyright All rights reserved
CATEGORY:
Research
SUBCATEGORY:
n/a
DATE – PUBLISHED:
2023-03-25T19:55:44Z
DATE – DOI: 2023-03-25T19:55:44Z
DATE – PUBMED: 2023 Mar 25
DATE OUTPUT MATCHED: True
DATE – ADDED:
Sat, 25 Mar 2023 06:00:00 -0400
DATE – RETRIEVED:
03/25/23 06:59PM
2023-03-25T18:59:21-04:00
FEATURED IMAGE:
Media Uploaded (image/png)
IDENTIFIER:
pmid:36965137,doi:10.1111/jns.12543
PUBMED ID:
pubmed:36965137
DOI:
10.1111/jns.12543
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/36965137/
LINK – DOI:
https://doi.org/10.1111/jns.12543
LINK – PUBLISHER:
https://onlinelibrary.wiley.com/doi/10.1111/jns.12543
REFERENCES:
CMT Treatment Report, Urgent Research, 2023-03-25T18:59:21-04:00, https://www.cmttreatmentreport.com.
