Interviews

The research projects of the “Neurodegenerative disease group” are for the moment exclusively focused on Huntington’s Disease (HD). This rare monogenic and neurodegenerative disease affects 1 : 10000 adult in Europe. HD symptoms are associated with the preferential loss of neurons in several regions of the brain (striatum & Cortex). Brain dysfunction begins at the adulthood; patients die usually 15 to 20 years later. Currently, no validated treatment of this disease exists.

Most if not all our research work is conducted using human embryonic stem cells (hESC) either normal or mutant, i.e carrying the mutation responsible for Huntington’s disease.  We strongly believe that this type of stem cells opens new prospects for research on HD. For example, we wish to develop the use of the human embryonic stem cells as substrate for HD cell therapy or the use of hESC carrying the Huntington mutation (hESC-HD) as cellular model to study HD pathological mechanisms. All our research projects have in common to take advantage of the extreme versatility and relevance of hESC and their progenies.

A cell therapy approach of Huntington’s disease via transplantation of fetal human cells coming from the ganglionic eminence has recently shown promising results demonstrating clinical benefits. However, the application of such treatment is restricted because the source of fetal cells, is limited, obtention of human fetal tissue requiring a chain of expertise that cannot be “industrialized”. For these reasons we chose in a very pragmatic way to try to replace foetal grafts by hESC-derived neural grafts; unlike fetal cells hESC are pluripotent and self-renewable. Concerning or work on the pathological modelling of HD we have also made the pragmatic choice of working with mutant hESC because they are for the moment and by far the more versatile and relevant type of stem cell at our disposal.

We hope that in the next ten years, the exploration of the molecular mechanisms of HD based on the use of hESC-HD will have helped to better understand this pathology and to identify major molecular targets against which I-Stem will have contributed to find therapeutic molecules.
We also wish that in the next ten years, hESC-derived neural graft for HD cell therapy will have been tested successfully on HD patients.