Principal investigators

CARDIFF UNIVERSITY    
IMG 1372Anne Rosser
(Coordinator)
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STEVEStephen Dunnett
(CO deputy)
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MENG2
Meng Li
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Nick 2Nicolas Allen
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PaulKPaul Kemp
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Monica
Monica Busse
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Liam
William Gray
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Expertise
Anne Rosser 
heads the all-Wales clinical neurology service for HD as consultant neurologist. She chairs the UK HD research network, the UK arm of the European HD Network, and is the lead for HD in the National Institute for Health Research's Dementia and Neurodegenerative Research Network (DeNDRoN). Her Cardiff-based HD research clinic participates in multiple epidemiological, pharmaceutical, and non-pharmaceutical trials, including the first systematic studies of directed exercise interventions in HD. She leads the UK HD clinical trial on safety and feasibility of foetal striatal cell transplants in HD. As a scientist, she co-directs the Brain Repair Group in Cardiff with particular responsibility for neural stem cell studies and is the clinical director of the Cardiff Foetal Tissue Bank.
Stephen Dunnett is the director of the Brain Repair Group in the School of Bioscience. e has an internationally recognised expertise in animal models of PD and HD, development of novel tests for analysis of cognitive and motor function in these rat and mouse models, systematic functional assessment of cell transplantation, and analysis of the mechanisms of functional recovery, as the basis for translational and preclinical development of methods for cell therapy in human neurodegeneration. His current research interest focuses on the functional organisation of the basal ganglia, and the development of effective cell-based therapies for neurodegenerative disease.
Meng Li has a long-standing interest in neural specification in PSC and pioneered the concept of genetic based lineage marking/selection of PSC-derived neural stem cells, which has become a generally adopted research strategy by stem cell and developmental biologists alike. Her research group has made significant contribution in uncovering the composition and the basic operational principles of gene regulation during PSC differentiation and developed novel methods that direct efficient differentiation of PSCs to defined neuronal subtypes for developing cell-replacement therapies as well as for building novel human ex vivo neuronal models of neurological diseases.
Paul Kemp has extensive experience electrophysiology and single cell imaging. He has established collaborations with several of the investigators at CU and collaborates widely and internationally. He is funded by the CHDI (with Nick Allen) to establish the functional correlates of transcription factor driven medium spiny neuron specification from hES and iPS (HD and control) cells.
Nick Allen has longstanding expertise in PSC differentiation and protocol development. He was amongst the first to develop chemically defined and scalable conditions for hES neural differentiation. The main focus of his lab is iPSC-based disease modelling of HD. This work includes protocol development for MSN differentiation and the development of in vitro assays for MSN function and dysfunction.
Monica Busse is an academic physiotherapist with specific expertise in physical interventions in HD and is a world leader in developing rehabilitation and training protocols for HD. She demonstrated the first evidence of muscle weakness in HD and the high risk of falls in this population. The group has also validated appropriate falls risk assessment outcome measures for this population and published a framework for physiotherapy intervention which has been adopted as a reference document by the European Huntington's Disease Network (EHDN) Physiotherapy Working Group of which she is co-lead facilitator.
William Gray heads the functional neurosurgery group at University Hospital Wales as a consultant neurosurgeon heand leads the surgical aspects of stereotactic transplantation studies in Cardiff. He recently moved to Cardiff from Southampton University where he established an internationally recognised group working on hippocampal neurogenesis. He is best known for his work on how neuropeptide neurotransmitters control the proliferation, survival and fate specification of endogenous neural stem cells. He has also developed novel 3D culture systems for culturing human adult cortical brain tissue resected during epilepsy surgery. 
Tasks in the project
Anne Rosser is the scientific coordinator of the Repair-HD consortium, with Stephen Dunnett as her deputy. In WP1, Meng Li has developed one of the primary protocols for differentiation of hPSCs to striatal fate and leads one of the two programmes for comparison, characterisation and validation of the differentiation of the alternative RC cell lines. Paul Kemp and Nick Allen lead the implementation of protocol characterisation by cellular physiology. Anne Rosser and Stephen Dunnett provide human foetal tissue to Roslin cells for GMP-ready iPS derivation. Stephen Dunnett leads WP2 with the primary focus of screening, characterisation and validation of alternative cells and protocols in vivo following transplantation in lesion and transgenic animal models, by functional motor and cognitive assessment, and by post mortem histological analysis of cell survival, differentiation and connectivity. This characterisation is complemented by Paul Kemp providing functional analysis at the cellular level by patch clamp physiology and calcium imaging in grafted striatal slices ex vivo, and William Gray providing hiSpot cultures for ex vivo culture of cells in adult human cortical slices. In WP4, Anne Rosser, Nick Allen and Stephen Dunnett provide validation and testing of protocols under GMP conditions. In WP5Anne Rosser is involved in the consensus definition and validation of a new CAPIT-HD protocol for patient assessment, and leads the specialist neurology research clinic within which one HD patient cohort will be recruited for test validation. In WP6, Anne Rosser, Stephen Dunnett, William Gray and Monica Busse contribute neurological, behavioural, physiotherapy and surgical expertise to the development of consensus protocols towards clinical trial design. In WP7, Anne Rosser, Stephen Dunnett and Liam Gray provide expertise and experience to the regulatory and ethical oversight and reviews of ongoing research programme and forthcoming trial readiness.
Team members
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Victoria Roberton - Expertise:
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 INSERM - U861/Institute for Stem cell therapy and exploration of monogenic diseases (I-Stem)
Anselme2
Anselme Perrier
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Expertise
Anselme Perrier has been working on hESC striatal differentiation and HD cell therapy since 2005. His team is using normal and disease-specific hPSCs for the understanding and treatement of HD.
His group is currently dedicated to the study of Huntington disease pathological mechanism, and to the development or validation of new therapeutic approach to HD (drug, gene and cell therapies). Website: I-Stem
Tasks in the project
Anselme Perrier is leading partner of WP1. In this WP the team will de
velop (i) a "Genomic integrity assay" for testing genomic alterations in graft preparation that may compromise their safety and (ii)  a "whole genome transcriptomic assay" based on high throughput RNA sequencing for unbiased quantification of phenotype and purity of striatal graft preparation. In close collaboration with Cardiff team, the group will contribute to the quantitative evaluation and ranking of the 3 protocols tested in WP1 according to predefined parameters and using GMP-grade hESC and later hiPSC products. In WP3 the team will be in charge of the timely production, transfer and cell handling for transplantation in HD monkey of PSC-derived allo- and xenograft in P3 and P4 labs. In WP4, the group will (together with the Cardiff team) be in charge of transferring the SOP and know-how on hPSC striatal differentiation to Roslin Cells and contribute to basic aspect of GMP-grade conversion of existing protocols.
Team members
 

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 Inserm - U955/Interventional Neuropsychology Laboratory   
Anne Cathereine 2Anne-Catherine
Bachoud-Levi
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Expertise
Anne-Catherine Bachoud-Levi is a neurologist with a specialisation in cognitive processing and biotherapy trial in HD. As a clinican, she heads the French National Reference Center for Huntington's disease and is one of the lead faciltators of the cognitive working group of the European Huntington's Disease Network (EHDN). As a researcher, she heads the "Interventional Neuropsychology" team devoted to the use of brain restoration as a model for understanding cognitive functions processing. She has led the clinical part of the pioneer demonstration of the clinical improvement provided by intracerebral cell therapy to HD patients. She is currently leading the international Multicentric intra-Cerebral Grafting in Huntington's disease (so called MIG-HD) which involves 45 HD patients already transplanted and thus has a unique experience in brain therapy trials in HD. Website: IMRB
Tasks in the project
Anne-Catherine Bachoud-Levi is leading WP5 and responsible for establishing the final CAPIT-HD 2, for the development of the cognitive testing. furthermore the group will participate to the establishment of the future guidelines for transplant with WP6.
Team members
This email address is being protected from spambots. You need JavaScript enabled to view it. - Expertise: Social cognition cognitive neuro-psychology, neuropsychology

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CEA   
Philippe
Philippe Hantraye
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Expertise
Philippe Hantraye's team has a long lasting experience in cell transplantation in the CNS and in animal models of neurodegenerative diseases, notably HD. The group has played a pioneer role in pre-clinical and clinical development and validation of therapeutic strategies for HD and Parkinson's disease (PD), including intrastriatal cell transplantation of striatal foetal cells in non-human primate models of HD and HD patients. Notabley, the group has developed and characterized most of the non-human primate models of HD available to date, including the excitotoxic striatal lesion that will be used in this proposal.
The team has extensive experience in the development of stateof- the-art imaging methods (PET, MRI or MRS) dedicated to the monitoring of brain functions in living beings (including non-human and human primates). Website: MIRCen
Tasks in the project
Philippe Hantraye is WP3 leader. The teams main task in this WP are: (i) determine survival, differentiation, growth and safety of grafted cells by in vivo imaging using a HD primate model as an optimal replicate of the human-to-human « clinical » scenario; (ii) xenografting hESC in non-human primates to identify surrogate markers of immune response and imaging; (iii) evaluate the functional recovery achieved by the best hESC identified by the consortium using the motor and cognitive tests.
Team members
This email address is being protected from spambots. You need JavaScript enabled to view it.  - Expertise: neurosurgery, behaviour

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CORIT   
Emanuele 2
Emanuele Cozzi
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Expertise
Emanuele Cozzi's group has developed an exceptional expertise in preclinical xenotransplantation models. In particular, the group is very familiar with the development of immunosuppressive regimens in the primate. Furthermore, through its close partnership with the CEA team, in the context of Xenome (a EU-funded Integrated Project), CORIT has developed an extensive know-how to enable successful xenotransplantation of neural precursor into the brain of Parkinsonian monkeys and functional monitoring and radio-imaging of xenografted primates.
Tasks in the project
Emanuele Cozzi's team will be involved in WP3: (1) xenotransplantation of hESC into non-human primates 2) efficacy studies using the motor and cognitive tests previously; (3) identification of surrogate markers of immune response in the same model.
Team members
Marta Vadori - Expertise: Immunology

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ROSLIN CELLS   
Paul2
Paul De Sousa
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Expertise
RC is certified to ISO9001:2008 and holds licenses from the UK Human Fertilisation and Embryology Authority and UK Human Tissue Authority. It is the first SME to produce clinical grade human embryonic stem cells (hESC) in Europe and is collaborating with others to use these to make clinical grade keratinocytes, endothelial cells and red blood cell concentrates for the treatment of skin ulcers, ischemia and transfusion respectively. RC's GMP Cellular Therapy Facility facility is licensed by the MHRA, having been awarded both a Manufacturer's and Importers Authorisation for Investigational Medicinal Products (MIA(IMP)) and a Manufacturer's 'Specials' license for Advanced Therapy Medicinal Products (ATMP).
This license allows Roslin Cells to manufacture clinical grade cellular therapy products, including GMP grade master banks of hESC, for clinical development. RC has built on this experience to establish an induced pluripotent stem cell (iPSC) cell core facility and service. Paul De Sousa is Chief Scientific Officer for Roslin Cells. His academic laboratory at the University of Edinburgh is focused on the use of human pluripotent stem cell in regenerative medicine and biotechnology.
Tasks in the project
In WP1, RC will create working banks of clinical grade hESC lines (3) for distribution to CU and INSERM A with standard operating procedures for local expansion and cryostorage to ensure a standardised supply of lines for MSN differentiation protocol development. Paul de Sousa will lead WP4 wherein it will define MSN product profile and GMP translation of an optimised differentiation protocol. It will also optimise and produce a working bank of up to 3 hiPSC lines using a GMP compatible protocol, which it will distribute to CU and INSERM A to evaluate for responsiveness to an optimised MSN differentiation protocol. It will also contribute its experience with regulatory authorities, ethical procurement of tissue and participation in multidisciplinary and national programs to WP5-7.
Team members
This email address is being protected from spambots. You need JavaScript enabled to view it. Expertise: Project managment
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UNIVERSITY OF MANCHESTER  
David
David Craufurd
Email
Expertise
David Craufurd is a Consultant Neuropsychiatrist based in the Genetic Medicine service at the Central Manchester University Hospitals NHS Trust. He is the lead clinician for HD in the North West of England, providing multidisciplinary HD management clinics and genetic counselling services for at-risk families in Greater Manchester and Lancashire, a catchment area with a population of 4.5 million. He is a member of the Executive Committee of the European Huntington's Disease Network, leads the EHDN Behavioural Phenotype Working Group, and is a Steering Committee member of Enroll-HD, a longitudinal observational study which is the core activity of EHDN and the equivalent research networks in North and South America, as well as some additional sites in Asia and Africa. His main research interests are the behavioural manifestations of HD, and the psychosocial impact of genetic testing for late-onset neurogenetic disorders. Website
Tasks in the project
In WP5, DC will participate in the consensus definition and validation of the new CAPIT-HD protocol for patient assessment, with particular responsibility for the neuropsychiatric assessments. He leads the specialist HD research clinic which will be one of the sites for beta-testing and validation of the new protocol. He will lead for WP6, and contribute clinical and neuropsychiatric expertise to the regulatory and ethical oversight of the research programme and preparation for future clinical trials
Team members
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GEORG HUNTINGTON INSTITUT  
Ralf2
Ralf Reilmann
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Expertise
Ralr Reilmann, GHI founder and director, has developed the Q-Motor assessments and is the Co-PI of the Q-Motor project in TRACK-HD and PREDICT-HD. Q-Motor systems are established in abt. 40 centers around the world and serve as endpoints in clinical trials in HD and PD. RR serves as global coordinating PI of two multicentre phase IIa clinical trials in EU/USA. In addition, he has been awarded and managed several grants & contract research projects for HD related research. He is active member of the Executive committee and the Clinical Trials Task Force of the EHDN and chair of the EHDN Motor and Neuroprotective Therapy Working Groups and serves on the scientific review committee of the ENROLL-HD study. Website
Tasks in the project
In WP5, Ralf Reilmann's team will participate in the consensus definition and validation of the new CAPIT-HD protocol for patient assessment, with particular responsibility for the Q-Motor (quantitative motor) assessments, developed in his group. He will assist in protocol development and evaluate clinical assessment tools for feasibility of application in clinical trials. Muenster will be one of the sites for beta-testing and validation of the new protocol. Ralf Reilmann leads WP7 and will contribute with project management experience and education and certification background to the successful establishment of research and clinical standards and training for the global project.
Team members
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INSERM TRANSFERT  
Christianemod
Christiane
Dascher-Nadel
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Expertise
Christiane Dascher-Nadel has extensive experience in both academic and industrial R&D research and has been active in the field of EC project management for the past ten years. She is heading a management team within Inserm Transfert's European Affairs department mainly focused on research projects related to stem cells and biotherapy.
Tasks in the project
Christiane Dascher-Nadel is leading WP7 – Project Management and Coordination. She will ensure a professional driving of the project, provide the partners with adequate communication tools and implement an appropriate strategy for knowledge management. In WP7 she will coordinate dissemination and communication activities.

Team members
Stéphanie Remola - Expertise: European projects manager
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