SUMMARY:
A recent study by Rizzo et al. has shown promising results in in vitro and in vivo models of the disease, but further research is needed to progress to clinical translation.
TITLE:
Charcot-Marie-tooth disease type 2A: An update on pathogenesis and therapeutic perspectives
DESCRIPTION:
Mutations in the gene encoding MFN2 have been identified as associated with Charcot-Marie-Tooth disease type 2A (CMT2A), a neurological disorder characterized by a broad clinical phenotype involving the entire nervous system. MFN2, a dynamin-like GTPase protein located on the outer mitochondrial membrane, is well-known for its involvement in mitochondrial fusion. Numerous studies have demonstrated its participation in a network crucial for various other mitochondrial functions, including…
CONTENT:
Neurobiol Dis. 2024 Mar 5:106467. doi: 10.1016/j.nbd.2024.106467. Online ahead of print.
ABSTRACT
Mutations in the gene encoding MFN2 have been identified as associated with Charcot-Marie-Tooth disease type 2A (CMT2A), a neurological disorder characterized by a broad clinical phenotype involving the entire nervous system. MFN2, a dynamin-like GTPase protein located on the outer mitochondrial membrane, is well-known for its involvement in mitochondrial fusion. Numerous studies have demonstrated its participation in a network crucial for various other mitochondrial functions, including mitophagy, axonal transport, and its controversial role in endoplasmic reticulum (ER)-mitochondria contacts. Considerable progress has been made in the last three decades in elucidating the disease pathogenesis, aided by the generation of animal and cellular models that have been instrumental in studying disease physiology. A review of the literature reveals that, up to now, no definitive pharmacological treatment for any CMT2A variant has been established; nonetheless, recent years have witnessed substantial progress. Many treatment approaches, especially concerning molecular therapy, such as histone deacetylase inhibitors, peptide therapy to increase mitochondrial fusion, the new therapeutic strategies based on MF1/MF2 balance, and SARM1 inhibitors, are currently in preclinical testing. The literature on gene silencing and gene replacement therapies is still limited, except for a recent study by Rizzo et al.(Rizzo et al., 2023), which recently first achieved encouraging results in in vitro and in vivo models of the disease. The near-future goal for these promising therapies is to progress to the stage of clinical translation.
PMID:38452947 | DOI:10.1016/j.nbd.2024.106467
SOURCE:
Neurobiology of disease
TAGS:
Rizzo et al
CATEGORY:
Research
SUBCATEGORY:
n/a
DATE – PUBLISHED:
2024-03-05T17:21:06Z
DATE – DOI: 2024-03-05T17:21:06Z
DATE – PUBMED: 2024 Mar 5
DATE OUTPUT MATCHED: True
DATE – ADDED:
Thu, 07 Mar 2024 06:00:00 -0500
DATE – RETRIEVED:
03/08/24 12:39AM
2024-03-08T00:39:52-05:00
FEATURED IMAGE:
Media Uploaded (image/jpeg)
IDENTIFIER:
pmid:38452947,doi:10.1016/j.nbd.2024.106467
PUBMED ID:
pubmed:38452947
DOI:
10.1016/j.nbd.2024.106467
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/38452947/
LINK – DOI:
https://doi.org/10.1016/j.nbd.2024.106467
LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S0969996124000664
REFERENCES:
CMT Treatment Report, Urgent Research, 2024-03-08T00:39:52-05:00, https://www.cmttreatmentreport.com.
