Effects of metformin on congenital muscular dystrophy type 1A disease progression in mice: a gender impact study
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/da2f62df-6a05-4bc7-a571-e7472978e464
- author
- Fontes Oliveira, Cibely LU ; M. Soares Oliveira, Bernardo LU ; Körner, Zandra LU ; Harandi, Vahid LU and Durbeej-Hjalt, Madeleine LU
- organization
- publishing date
- 2018-11-02
- 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}}, }