CMTX1 patients' cells present genomic instability corrected by CamKII inhibitors.

Abstract

BACKGROUND:

We previously described that fibroblasts from animal models of CMTX1 present genomic instability and poor connexon activity. In vivo, these transgenic mice present motor deficits. This phenotype could be significantly reverted by treatment with (CamKII) inhibitors. The objective of this study is to translate our findings to patients.

METHODS:

We cultured fibroblasts from skin biopsies of CMTX1 patients and analyzed cells for genomic instabilty, connexon activity, and potential correction by CamKII inhibitors.

RESULTS:

The phenotypic analysis of these cells confirmed strong similarities between the GJB1 transgenic mouse cell lines and CMTX1 patient fibroblast cell lines. Both present mitotic anomalies, centrosome overduplication, and connexon activity deficit. This phenotype is corrected by CamKII inhibitors.

CONCLUSIONS:

Our data demonstrate that fibroblasts from CMTX1 patients present a phenotype similar to transgenic lines that can be corrected by CamKII inhibitors. This presents a track to develop therapeutic strategies for CMTX1 treatment.

• Authors: Saleh Mones, Burkhardt Gess, Benoit Bordignon, Alexandre Altié, Peter Young, Frederic Bihel, Marc Fraterno, Franck Peiretti, Michel Fontes, Mones Saleh, Gess Burkhardt, Bordignon Benoit, Altié Alexandre, Young Peter, Bihel Frederic, Fraterno Marc, Peiretti Franck, Fontes Michel
• Journal: Orphanet journal of rare diseases (Orphanet J Rare Dis) Vol. 10 Pg. 56 (May 07 2015) ISSN: 1750-1172 [Electronic] England
• PMID: 25947624 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Calcium-Calmodulin-Dependent Protein Kinase Type 2

Topics

• Adolescent
• Adult
• Animals
• Calcium-Calmodulin-Dependent Protein Kinase Type 2 (antagonists & inhibitors)
• Cell Line
• Charcot-Marie-Tooth Disease (genetics)
• Enzyme Inhibitors (pharmacology)
• Female
• Fibroblasts (drug effects, metabolism)
• Genomic Instability (drug effects, genetics)
• Humans
• Male
• Mice
• Young Adult