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This Eu funded Consortium took human stem cells through the final steps toward clinical application in cell replacement therapy for neurological disorders, such as Parkinson’s Disease, taken as the prototypical disease. Moreover, the project tackled next issues pertaining to stem cells at a basic level and developed new approaches and novel cell sources, validated at pre-clinical stages for both Parkinson’s Disease and Huntington’s Disease. The project teams represented a wide range of competences, including stem cell specialists, developmental neurobiologists, experts in neurodegeneration, scientists with links to the clinic and stem cell manufacturing/clinical validation.
The research plan addressed issues related to the control of progenitor cells proliferation and differentiation into authentic, functional and phenotypically stable dopaminergic or striatal neurons, and exploited new technology for cell reprogramming. The project also developed strategies to obtain endurable donor cell engraftment in the host, including acquisition of specific neuronal identities and functional integration in the recipient brain
Transeuro is a European research consortium with the principal objective to develop an efficacious and safe treatment methodology for Parkinson’s disease suffering patients using fetal cell based treatments. The consortium has gathered international experts including leading clinicians, scientists, industrial partners, ethicists and patients’ representatives who have joined forces in a new round of experimental work and cell therapy trials in Parkinson’s Disease.
There are currently no cures for Parkinson's disease but one of the most effective reparative therapies in patients to date has been with allotransplants of dopamine neuroblasts obtained from fetal ventral mesencephalic tissue. However, this cell transplantation approach has given inconsistent results, with some patients doing extremely well and coming off anti-PD medication for years, whilst others have shown no or only modest clinical improvements, and in some cases also developed severe, off-state graft-induced dyskinesias (GIDs). TRANSEURO investigated the heterogeneity of outcomes, and the emergence of GIDs in particular, in the perspective of the rapid advances that are now being made in the development of stem-cell based therapies and with the expectation that a critical reassessment of forme trials can form the basis for an optimised and more standardised procedure that will translate into more consistently efficacious transplants with minimal side-effects.
Therefore, a group of international experts, including the key investigators of the previous European and North American trials, re-examined the outcome of these trials as well as reviewed the results obtained from animal experimental studies, and identified a number of weaknesses that may explain the inconsistent outcome in previous trials. As a result of these discussions, the group joined forces in a new round of experimental work and cell therapy trials in PD, based on a new jointly developed protocol where all these factors are taken into account.
The project tackled the huge complexity of taking stem cell therapies to clinical application for neurodegenerative disease by focusing on selective differentiation of a single neuronal phenotype (medium spiny striatal neuron: MSN) for a single well-defined disease (Huntington’s: HD). This consortium focussed on human embryonic stem (hES) cells as their primary target for first-in-man proof-of-concept studies, as they are closest to clinical readiness. One important feature of this consortium was that the specificity of stem cell differentiation was tested against primary fetal MSNs (current gold standard) at all stages of both in vitro and in vivo assessment.