Project

preclinical; cell therapy; Parkinson's disease; embryonic stem cells; dopaminergic neurson; safety

Lead
Lay summary
Parkinson's disease (PD) is a devastating neurodegenerative disease. The main symptoms of the patient are linked to mobility and the term "shaking palsy" is also used for the disease. Available treatment for Parkinson's disease are capable of improving symptoms for a limited period of time, but presently no cure is available. The cause of Parkinson's disease is the loss of a certain type of nerve cells in the brain, in particular the so-called "dopaminergic neurons. It is the long term aim of our project to implant dopaminergic neurons, generated from embryonic stem cells, into damaged brain areas of patients with Parkinson's disease. The PROMETHEUS consortium proposes to address key issues for a successful transfer of the concept into clinical studies. Six different groups will work together synergistically to i) optimize production of dopaminergic neurons from embryonic stem cells, ii) to test these cells as therapeutics in animal models, iii) to develop strategies that minimize the risk or tumor formation from implanted cells, iv) to develop strategies to avoid immune rejection, v) to follow a patient cohort in preparation of a first clinical study, and vi) to analyze ethical issues concerning all aspects of the proposal (stem cell generation, animal experimentation and first patient studies). If successful, the PROMETHEUS consortium should provide important new tools for the treatment of Parkinson's disease

Direct link to Lay Summary

Last update: 21.02.2013

Communication	Title	Media	Place	Year

Number	Title	Start	Funding scheme

Parkinson's disease (PD) is a devastating neurodegenerative disease. Although the neuropathology is widespread in advanced disease, the motor symptoms appear to be mostly due to the loss of dopaminergic neurons in the substantia nigra. Given the relative importance of this specific cell loss, PD is considered as a promising target for cell therapy. The potential of pluripotent stem cells, PSCs, (i.e. embryonic stem cells and - possibly on the long - run induced pluripotent stem cells) to generate high quality dopaminergic neurons in vitro and their efficiency to improve symptoms in rodent and primate models of PD has been well documented (1). However, there is a considerable gap between successful laboratory research in this domain and the progress towards a clinical application. It is the aim of the Prometheus project to bridge the gap between the present research and future applications in humans. For this purpose, close collaborations between experts from diverse areas are required: clinicians (neurologists, neurosurgeons, radiologists, immunologists, infection control experts), laboratory based researchers (animal experimentation; cell biologists), as well as biomedical ethicists. The Prometheus consortium consists of seven closely collaborating groups that will cover the major preclinical challenges of PD cell therapy. Group 1 will produce clinical grade dopaminergic neurons from human embryonic stem cells. Group 2 will test cells produced by G1 in rodent and primate models and investigate the role of PET imaging as in-vivo follow-up of transplanted cells. Group 3 will focus on strategies of tumor/teratoma prevention. Group 4 will study immune reactions towards transplanted cells and advise G2 and G6 on immunosuppressive therapies. Group 5 will coordinate infection control and quality assurance and will provide advise and microbiological testing for G1, G2 and G6. Group 6 will integrate the information received from all other groups and define base-line parameters through a pre-study follow-up of PD patients, as well as establish a clinical protocol for patient selection and determine the best neurosurgical procedure. Group 7 will work on ethical aspects of the cell and animal studies, as well as all ethical prerequisites for the initial clinical studies. The ultimate goal of the project is to advance towards a cell therapy for PD under conditions that fully integrate experimental science, patient security and biomedical ethics. Only an interdisciplinary team, such as the one assembled for this project will be able to meet this challenge. To our understanding, no such comprehensive approach to the problem is presently implemented in other places. This should give the Prometheus team a leading edge in the development of a safe and ethical development of cell therapy for PD.