SUMMARY:
CX201 administration improved the demyelinating phenotypes of CMT1A mouse models at both pre-symptomatic and post-symptomatic stages. These results suggest that the TGFβ4/Nodal axis plays a crucial role in the pathogenesis of CMT1A and might be a potential therapeutic target for CMT1A.
TITLE:
TGFβ4 alleviates the phenotype of Charcot-Marie-Tooth disease type 1A
DESCRIPTION:
The duplication of the peripheral myelin protein 22 (PMP22) gene causes a demyelinating type of neuropathy, commonly known as Charcot-Marie-Tooth disease type 1A (CMT1A). Development of effective drugs for CMT1A still remains as an unmet medical need. In the present study, we assessed the role of the transforming growth factor beta 4 (TGFβ4)/Nodal axis in the pathogenesis of CMT1A. First, we identified PMP22 overexpression-induced Nodal expression in Schwann cells (SCs), which might be one of…
CONTENT:
Brain. 2023 May 5:awad147. doi: 10.1093/brain/awad147. Online ahead of print.
ABSTRACT
The duplication of the peripheral myelin protein 22 (PMP22) gene causes a demyelinating type of neuropathy, commonly known as Charcot-Marie-Tooth disease type 1A (CMT1A). Development of effective drugs for CMT1A still remains as an unmet medical need. In the present study, we assessed the role of the transforming growth factor beta 4 (TGFβ4)/Nodal axis in the pathogenesis of CMT1A. First, we identified PMP22 overexpression-induced Nodal expression in Schwann cells (SCs), which might be one of the downstream effector in CMT1A. Administration of Nodal protein at the developmental stage of peripheral nerves induced the demyelinating phenotype in vivo. Second, we further isolated TGFβ4 as an antagonist that could abolish Nodal-induced demyelination. Finally, we developed a recombinant TGFβ4-fragment crystallizable (Fc) fusion protein, CX201, and demonstrated that its application had promyelinating efficacy in SCs. CX201 administration improved the demyelinating phenotypes of CMT1A mouse models at both pre-symptomatic and post-symptomatic stages. These results suggest that the TGFβ4/Nodal axis plays a crucial role in the pathogenesis of CMT1A and might be a potential therapeutic target for CMT1A.
PMID:37143322 | DOI:10.1093/brain/awad147
SOURCE:
Brain : a journal of neurology
TAGS:
CX201
CATEGORY:
Research
SUBCATEGORY:
n/a
DATE – PUBLISHED:
2023-05-05T05:15:23Z
DATE – DOI: 2023-05-05T05:15:23Z
DATE – PUBMED: 2023 May 5
DATE OUTPUT MATCHED: True
DATE – ADDED:
Fri, 05 May 2023 06:00:00 -0400
DATE – RETRIEVED:
05/05/23 06:38AM
2023-05-05T06:38:22-04:00
FEATURED IMAGE:
Media Uploaded (image/png)
IDENTIFIER:
pmid:37143322,doi:10.1093/brain/awad147
PUBMED ID:
pubmed:37143322
DOI:
10.1093/brain/awad147
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37143322/
LINK – DOI:
https://doi.org/10.1093/brain/awad147
LINK – PUBLISHER:
https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awad147/7152691
REFERENCES:
CMT Treatment Report, Urgent Research, 2023-05-05T06:38:22-04:00, https://www.cmttreatmentreport.com.
