Support our Foundation of Myology project
Towards a new therapeutic approach to cardiovascular complications in progeria?
Partager sur
Hutchinson-Gilford syndrome (HGPS or progeria) is an autosomal dominantEn génétique, c’est la caractéristique d’un individu qui n’a besoin que d’un seul exemplaire d’un certain gène (allèle) pour s’exprimer. Cet exemplaire unique peut venir du père ou de la mère. disease caused by a mutationModification soudaine et transmissible du matériel génétique. Elle peut être spontanée ou induite par des agents dits » mutagènes » (radiations, produits toxiques,…). in the LMNA gene, coding for type A lamins, which results in a truncated form of pre-lamin A called progerin. Although asymptomatic at birth, patients develop symptoms such as accelerated ageing, growth retardation and loss of vascular smooth muscle cells (VSMC) during the first year of life.
In this article, researchers from Antoine Muchir’s team* at the Institut de Myologie, in collaboration with Xavier Nissan’s (I-Stem) and Nicolas Lévy’s (Marseille) teams, investigated the mechanisms by which progerin expression leads to massive VSMC loss.
Using aorta tissue, primary cultures of mouse VSMCs from a mouse model of HGPS, and induced pluripotent stem cells (iPS) from patients, the authors :
- demonstrated the link between progerin accumulation, increased poly(ADP-Ribosyl)ation and decreased nicotinamide adenine dinucleotide (NAD+) levels in VSMCs,
- identified a new compound, trifluridine, capable of increasing NAD+ levels by decreasing the activity of poly-ADP-ribose polymerase (PARP-1), which catalyzes the poly(ADP-Ribosyl)ation of proteins with NAD+,
- showed that trifluridine treatment in vivoDans le vivant, à l’intérieur de l’organisme. was able to attenuate the loss of aortic VSMCs and the clinical signs of progeria.
These results suggest a new therapeutic approach to cardiovascular disease in progeria patients.
*Signaling pathways and & striated muscles team at the Center of Research in Myology