Interview Geneviève Piétu

Geneviève Piétu, Research Director INSERM

Principal Investigator "Neuromuscular diseases Team"

1. On which pathology is your research focused on I-Stem ?

Our team works on Myotonic Dystrophy type 1 (DM1) or Steinert disease.
The Steinert disease is characterized by a progressive dystrophy (weakness and muscular atrophies) associated with a myotonia ((delayed muscle relaxation after voluntary contraction). This pathology is related to an expanded trinucleotide repeat (CTG)n situated in the 3’-untranslated region (3’-UTR) of the Dystrophy Myotonic Protein Kinase (DMPK) gene. The enlarged CUG-containing transcripts that accumulate as foci in the nuclei of both cultured cells and biopsy tissue could exert a trans-dominant effect that disrupts splicing and possibly other cellular functions. This mechanism would explain the diversity of the affected cellular types as well as various clinical disorders observed: myotony, cataract, central nervous system deteriorations, cardiac conduction abnormalities, diabetus, etc….

2. What are your expectations from stem cells within your research area ?

The objective of our research program is to use human ES cell lines, derived from embryos characterized as gene-carriers following pre-implantation genetic diagnosis (PGD), to carry out a pathological modelling of rare monogenic diseases by reproducing the molecular defects associated to the pathology.
These cells could also be useful for the screening of potentially therapeutic molecules able to interfere with molecular and cellular abnormalities induced by the mutation, either to look to their mechanisms of action or to determine their toxicity.
In order to evaluate the feasibility and validate our scientific concept, we are using as a “model” the Myotonic Dystrophy type 1 (DM1) or Steinert disease, for which we have access to an already available derived hES cell line expressing a mutant gene at the origin of DM1 and derived in the laboratory of Andre van Steirteghem in Brussels. This mutant hES cell line was imported in our laboratory in August 2005.

3. What is specifically relevant in hES cells research ?

The hES cell line carrying the DM1 mutation constitutes a valuable in vitro tool to study the physiopathological mechanisms implied in this pathology which remain still badly understood to date.
These hES cells, in addition of their ability to propagate indefinitely, representing an unlimited source of cells, will keep the mutation characteristics during time, which is not the case for example of the classical muscular cell models which have very limited survival times in culture.
Moreover, the capacity of the hES cells to differentiate into all lineages towards various cellular types, for example neural or myogenic, will make it possible to decline a diversity of cell phenotypes and several stages of differentiation in order to explore several aspects of the clinical symptoms associated to the pathology.

4. Which aims are you expecting to reach within the next 10 years ?

This project should lead to the establishment of a list of dysfunctions and deteriorations which affect specifically the cells expressing the DM1 mutation. We will be able to reveal, the genes or the proteins implied in these deteriorations that will give us keys for the molecular mechanisms implicated in the development of this pathology and the identification of potential therapeutic compounds able to be opposed to their dysfunction. It will open the way to new therapeutic developments.

 

 

<< Retour à la liste