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Effects of metformin on congenital muscular dystrophy type 1A disease progression in mice: a gender impact study

Fontes Oliveira, Cibely LU ; M. Soares Oliveira, Bernardo LU orcid ; Körner, Zandra LU ; Harandi, Vahid LU and Durbeej-Hjalt, Madeleine LU (2018) In Scientific Reports
Abstract
Congenital muscular dystrophy with laminin α2 chain-deficiency (LAMA2-CMD) is a severe muscle disorder with complex underlying pathogenesis. We have previously employed profiling techniques to elucidate molecular patterns and demonstrated significant metabolic impairment in skeletal muscle from LAMA2-CMD patients and mouse models. Thus, we hypothesize that skeletal muscle metabolism may be a promising pharmacological target to improve muscle function in LAMA2-CMD. Here, we have investigated whether the multifunctional medication metformin could be used to reduce disease in the dy2J/dy2J mouse model of LAMA2-CMD. First, we show gender disparity for several pathological hallmarks of LAMA2-CMD. Second, we demonstrate that metformin treatment... (More)
Congenital muscular dystrophy with laminin α2 chain-deficiency (LAMA2-CMD) is a severe muscle disorder with complex underlying pathogenesis. We have previously employed profiling techniques to elucidate molecular patterns and demonstrated significant metabolic impairment in skeletal muscle from LAMA2-CMD patients and mouse models. Thus, we hypothesize that skeletal muscle metabolism may be a promising pharmacological target to improve muscle function in LAMA2-CMD. Here, we have investigated whether the multifunctional medication metformin could be used to reduce disease in the dy2J/dy2J mouse model of LAMA2-CMD. First, we show gender disparity for several pathological hallmarks of LAMA2-CMD. Second, we demonstrate that metformin treatment significantly increases weight gain and energy efficiency, enhances muscle function and improves skeletal muscle histology in female dy2J/dy2J mice (and to a lesser extent in dy2J/dy2J males). Thus, our current data suggest that metformin may be a potential future supportive treatment that improves many of the pathological characteristics of LAMA2-CMD. (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
MDC1A; Gender; Metformin
in
Scientific Reports
article number
16302
pages
15 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85055998227
  • pmid:30389963
ISSN
2045-2322
DOI
10.1038/s41598-018-34362-2
language
English
LU publication?
yes
id
da2f62df-6a05-4bc7-a571-e7472978e464
date added to LUP
2018-11-05 12:33:28
date last changed
2022-03-25 05:27:10
@article{da2f62df-6a05-4bc7-a571-e7472978e464,
  abstract     = {{Congenital muscular dystrophy with laminin α2 chain-deficiency (LAMA2-CMD) is a severe muscle disorder with complex underlying pathogenesis. We have previously employed profiling techniques to elucidate molecular patterns and demonstrated significant metabolic impairment in skeletal muscle from LAMA2-CMD patients and mouse models. Thus, we hypothesize that skeletal muscle metabolism may be a promising pharmacological target to improve muscle function in LAMA2-CMD. Here, we have investigated whether the multifunctional medication metformin could be used to reduce disease in the dy2J/dy2J mouse model of LAMA2-CMD. First, we show gender disparity for several pathological hallmarks of LAMA2-CMD. Second, we demonstrate that metformin treatment significantly increases weight gain and energy efficiency, enhances muscle function and improves skeletal muscle histology in female dy2J/dy2J mice (and to a lesser extent in dy2J/dy2J males). Thus, our current data suggest that metformin may be a potential future supportive treatment that improves many of the pathological characteristics of LAMA2-CMD.}},
  author       = {{Fontes Oliveira, Cibely and M. Soares Oliveira, Bernardo and Körner, Zandra and Harandi, Vahid and Durbeej-Hjalt, Madeleine}},
  issn         = {{2045-2322}},
  keywords     = {{MDC1A; Gender; Metformin}},
  language     = {{eng}},
  month        = {{11}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Effects of metformin on congenital muscular dystrophy type 1A disease progression in mice: a gender impact study}},
  url          = {{http://dx.doi.org/10.1038/s41598-018-34362-2}},
  doi          = {{10.1038/s41598-018-34362-2}},
  year         = {{2018}},
}