 Our group was launched as an independent lab in
2003 with the support of the Avenir program (INSERM). We have an internationally
acknowledge expertise in the field of early- onset myopathies (EOM), which are
heterogeneous, inherited muscle disorders presenting with muscle weakness from
birth or early infancy. We develop a multidisciplinary approach to the study of
EOM, situated at the interface clinical/basic research. In the last years,
thanks to a collaborative strategy, we defined a line of research on EOM,
created and animated a European network which provided a critical mass of
patients, identified that mutations in 4 genes are responsible for 8 forms of
EOM, reassessed the corresponding phenotypes and contributed to establish a
new, genetically-based nosological classification in this field. Currently, we
focus on getting a better knowledge of the mechanisms leading from the genetic
defects in EOM to the phenotypical consequences in patients, in order to
develop pathophysiology-based therapeutic approaches, namely pharmacological
therapies. Particularly, we established or contributed to establish that
mutations of the SEPN1 gene, encoding selenoprotein N (SelN), are responsible
for 4 categories of EOM. Using an exvivo model (cultured cells from patients),
we have recently established that oxidative/nitrosative stress is implicated in
the pathophysiology of SEPN1-related myopathy, and that antioxidants are an
effective ex-vivo treatment. Oxidative stress induces epigenetic modifications
in stem cells, and preliminary data obtained by other groups suggest a
modulation of satellite cell markers by SelN. We are interested in characterizing
further these mechanisms, and also the mechanistic links between oxidative
stress, the severe muscle atrophy observed in patients with SEPN1 mutations and
the modulation of expression of genes involved in cell survival and death, We
will develop additional pharmacological studies ex-vivo and on the animal model
of SelN deficiency, to analyze the effects of antioxidants on the pathways
mentioned above. A first clinical trial of SEPN1-related myopathy with
antioxidants is being designed. |
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Myology Group Marie Curie Paris VI UMR S 787 - UPMC Paris VI 105 bd de l'Hôpital 75634, Paris Cedex 13 |
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