Intra-cerebral transplant can provide some functional benefit to patients suffering from neurological disorders in particular when neurodegeneration is localised and affects a limited number of neuronal subtypes as for patients suffering from Parkinson’s or Huntington’s disease.
Homotypic neuronal progenitors derived from human pluripotent cells (embryonic or reprogrammed) represent a therapeutic alternative to fetal tissues, the use of which remains complicated, as revealed by clinical trials already published or in progress.
However, to make the use of stem cells for cell therapy commonplace, the factors predicting the success of these transplants in patients, which are still difficult to assess, must be rapidly identified.
Over the past decade, clinical trials have provided evidence of the benefit of foetal neuron transplantation in neurodegenerative diseases therapy in particular in Huntington’s and Parkinson’s diseases.
In this field, “Multicentric Intracrebral Grafting in Huntington‘s disease” remains the most advanced program currently conducted (A.-C. Bachoud-Levi) : MIG-HD
has already enrolled 46 transplanted patients in various centres in France and Belgium with a mean follow-up duration of 5 years.
This work has highlighted some of the challenges to be overcome in future clinical trials. It also demonstrated the feasibility and potential therapeutic efficacy of these intracerebral transplantation approaches, paving the way for new cell therapy strategies for Huntington's disease and other brain diseases.
In parallel, several researh teams have explored the potential of human pluripotent stem cells (hPSCs) for intracerebral grafts
. The aim is to assess their therapeutic potential both in vitro and in small and large animal models as well as the safety issues raised by the use of hPSC 1-3 in humans.The objective of the NeurAtris research program « Cellular therapies » is to develop new methodologies to foster the translation of successful experimental cell therapies for neurological disorders to the clinic and to determine how to improve this therapies.
The methodological developments implemented concern :
- At the preclinical level: on the quality control of grafts derived from research-grade stem cells, and their conversion into cells usable in in vitro and in vivo clinical trials,
- At the clinical level: on immunological and neurological issues, data processing, regulatory and ethical issues specific to phase I and II clinical trials using pluri- and/or multi-potent stem cell derivatives.