Résumé :
|
Laminopathies include a wide range of heterogeneous diseases involving different tissues, ranging from isolated peripheral neuropathies to systemic, premature aging diseases as Hutchinson-Gilford Progeria. Since the first involvement of the LMNA gene, encoding Lamins A/C, in autosomal dominant or recessive Emery-Dreifuss muscular dystrophy in 1999, clinical and fundamental research have progressed in parallel, allowing to put the basis for the discovery of more than 10 different heritable diseases linked to primary or secondary Lamin A/C dysfunction. As a direct consequence, genetic counselling and follow-up of affected families has been greatly improved. Many different “laminopathic” animal models have been developed, often helping to guide clinicians into the “candidate laminopathy” search in human. In the last few years, the study of patients’ biological samples and of animal models has allowed to identify some major pathophysiological molecular pathways involved in Lamin-linked diseases. In particular, in progeroid syndromes linked to altered Lamin A post-translational processing, a major pathophysiological actor, exerting toxic effects at the cell, organ and whole body levels, has been identified. Different therapeutic strategies targeting this toxic molecule have thus being tested on animal models, with positive biological results, opening the way for clinical trials on patients. One of these trials has started, another is in preparation: both represent a great hope for the families affected by these rare but terrible disorders and the scientific community.
|