preclinical; cell therapy; Parkinson's disease; embryonic stem cells; dopaminergic neurson; safety
Casimir de Rham, Tieng Vannary, Tournier Benjamin, Avila Yannick, Ginovart Nathalie, Krause Karl-heinz, Preynat-Seauve Olivier, Dubois-Dauphin Michel, Villard Jean (2014), The Role of Immunosuppression in the Transplantation of Allogenic Neural Precursors Derived from Human Pluripotent Stem Cells for Parkinson’s Disease, in Stem Cell Research & Therapy
Kaeser Mélanie, Chatagny Pauline, Gindrat Anne-Dominique, Savidan Julie, Badoud Simon, Fregosi Michela, Moret Véronique, Roulin Christine, Rouiller Eric M, Schmidlin Eric (2014), Variability of manual dexterity performance in non-human primates (Macaca fascicularis)
, International Journal of Comparative Psychology, USA.
Gindrat Anne-Dominique, Quairiaux Charles, Britz Juliane, Brunet Denis, Lanz Florian, Michel Christoph M, Rouiller Eric M (2014), Whole-scalp EEG mapping of somatosensory evoked potentials in macaque monkeys., in Brain structure & function
, May 4. [Epub ahead of print] PubMed PMID: 24791748, 1-22.
Chatagny Pauline, Badoud Simon, Kaeser Mélanie, Gindrat Anne-Dominique, Savidan Julie, Fregosi Michela, Moret Véronique, Roulin Christine, Schmidlin Eric, Rouiller Eric M (2013), Distinction between hand dominance and hand preference in primates: a behavioral investigation of manual dexterity in nonhuman primates (macaques) and human subjects., in Brain and behavior
, 3(5), 575-95.
Gilbert F, Vranic A, Hurst SA (2013), Involuntary & Voluntary Invasice Brain Surgery : Ethical Issues Related to Acquired aggressiveness., in Neuroethics
, 6( 1), 115-128.
Martinez Y, Béna F, Gimelli S, Tirefort D, Dubois-Dauphin M, Krause K-H, Preynat-Seauve O (2012), Cellular diversity within embryonic stem cells: Pluripotent clonal sublines show distinct differentiation potential, in Journal of Cellular and Molecular Medicine
, 16(3), 456-467.
Barazzetti G, Hurst SA, Mauron A (2012), Clinically Driven Safety Benchmarks, in AJOB Neuroscience
, 3(2), 22-23.
Martinez Yannick, Dubois-Dauphin Michel, Krause Karl-Heinz (2012), Generation and applications of human pluripotent stem cells induced into neural lineages and neural tissues, in Frontiers in Physiology
, 3 MAR, 3-47.
Zimmermann A, Preynat-Seauve O, Tiercy J-M, Krause K-H, Villard J (2012), Haplotype-based banking of human pluripotent stem cells for transplantation: Potential and limitations, in Stem Cells and Development
, 21(13), 2364-2373.
de Rham Casimir, Villard Jean (2011), How to cross immunogenetic hurdles to human embryonic stem cell transplantation., in Seminars in immunopathology
, 33(6), 525-34.
Preynat-Seauve O, Krause K-H (2011), Stem cell sources for regenerative medicine: The immunological point of view, in Seminars in Immunopathology
, 33(6), 519-524.
Zhang J, Lu J-P, Suter DM, Krause K-H, Fini ME, Chen B, Lu Q (2010), Isoform- and dose-sensitive feedback interactions between paired box 6 gene and δ-catenin in cell differentiation and death, in Experimental Cell Research
, 316(6), 1070-1081.
Baertschi B, Hurst SA, Mauron A (2010), It's not who you are, in AJOB Neuroscience
, 1(3), 18-19.
Kuegler PB, Zimmer B, Waldmann T, Baudis B, Llmjarv S, Hescheler J, Gaughwin P, Brundin P, Mundy W, Bal-Price AK, Schrattenholz A, Krause KH, Van Thriel C, Rao MS, Kadereit S, Leist M (2010), Markers of murine embryonic and neural stem cells, neurons and astrocytes : reference po0ints for developmental neurotixicity testing., in ALTEX
, 27(1)(27(1)), 17-42.
Dubois-Dauphin Michel, Julien Stéphanie (2010), Stem cell-derived neurons grafted in the striatum are expelled out of the brain after chronic cortical stroke., in Stroke; a journal of cerebral circulation
, 41(8), 1807-14.
Dubois-Dauphin Michel L, Toni Nicolas, Julien Stéphanie D, Charvet Igor, Sundstrom Lars E, Stoppini Luc (2010), The long-term survival of in vitro engineered nervous tissue derived from the specific neural differentiation of mouse embryonic stem cells., in Biomaterials
, 31(27), 7032-42.
Preynat-Seauve Olivier, de Rham Casimir, Tirefort Diderik, Ferrari-Lacraz Sylvie, Krause Karl-Heinz, Villard Jean (2009), Neural progenitors derived from human embryonic stem cells are targeted by allogeneic T and natural killer cells., in Journal of cellular and molecular medicine
, 13(9B), 3556-69.
Suter DM, Preynat-Seauve O, Tirefort D, Feki A, Krause K-H (2009), Phenazopyridine induces and synchronizes neuronal differentiation of embryonic stem cells, in Journal of Cellular and Molecular Medicine
, 13(9 B), 3517-3527.
Preynat-Seauve Olivier, Burkhard Pierre R, Villard Jean, Zingg Walter, Ginovart Nathalie, Feki Anis, Dubois-Dauphin Michel, Hurst Samia A, Mauron Alex, Jaconi Marisa, Krause Karl-Heinz (2009), Pluripotent stem cells as new drugs? The example of Parkinson's disease., in International journal of pharmaceutics
, 381(2), 113-21.
Tieng Vannary, Stoppini Luc, Villy Sabrina, Dubois-Dauphin Michel, krause Karl-heinz, Fathi Marc, Engineering of Midbrain Organoids Containing Long-Lived Dopaminergic Neurons., in Stem Cells Dev
, Volume 00, (Number 00).
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.