Development and validation of functional cell therapies for Huntington's and Parkinson's diseases

Lead Research Organisation: Cardiff University
Department Name: School of Medicine

Abstract

Involving neural tissue transplantation in the brain, as well as stem cells, human embryos and animal experiments, this research is high profile in the general as well as scientific news media. In addition to publication in peer reviewed journals, the results of the present project will be widely disseminated to the biomedical research community, to NHS and clinical professions, and to interested charities and the lay public, through lectures and seminars in the normal way as well as in media interviews when appropriate. The PIs already have extensive experience in public communication of research results. We strive to achieve the best balance between the competing demands of proper disclosure of publicly funded science, public education, promoting enthusiasm for science and support for the MRC and biomedical research, but without raising false or premature hopes for cures that remain distant. The credibility of the team is enhanced by the close collaboration of the two PIs, one a basic scientist and the other a clinical scientist, combining resources and expertise to develop a translational programme for novel cell-based treatments for crippling human neurodegenerative diseases, spanning basic cellular, molecular and behavioural science through to clinical delivery in patients.

Technical Summary

The UK is taking an international lead in developing stem cells for cell-based therapy applicable to a broad range of diseases. However, for these new sources of cells to come to effective application in the clinic requires that they are first evaluated and validated for specificity and functional potential in appropriate model systems, both in vitro and in vivo.

The proposed project establishes quality-controlled processing of cells in vitro, determines optimal dissection, preparation handling and transplantation protocols, develops the experimental models for functional analysis, and refines our understanding of the theoretical principles and mechanisms of function for application of cell-based therapies in two specific human neurodegenerative diseases, Huntington‘s and Parkinson‘s. The programme sustains a centre of expertise developing the quality-controlled facilities necessary to progress specific cell sources (fetal now, expanded progenitors imminently, and stem cells in the foreseeable future) to clinical application rapidly and efficiently.

Publications

10 25 50
 
Description Citations in clinical guidelines and reviews
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical reviews
Impact we contribute to ongoing debate and updating of guidelines on ethical sourcing of human fetal tissues for research and clinical cell transplantation.
 
Description GTAC
Geographic Reach National 
Policy Influence Type Participation in a national consultation
Impact development of national ethical and regulatory guidelines
 
Description GTAC
Geographic Reach National 
Policy Influence Type Participation in advisory committee
Impact member of GTAC committee reviewing applications and developing policy on stem cell and gene therapy trials in the UK
 
Description MRC
Geographic Reach National 
Policy Influence Type Participation in advisory committee
Impact Targetted direction, policy and funding of UK stem cell research .
 
Description MRC Stem Cells
Geographic Reach National 
Policy Influence Type Participation in advisory committee
Impact I participate in the MRC UK Stem Cell Bank users group and contribute regularly to the policy discussions at head office on stem cell strategy and funding.
 
Description MRC stem cell
Geographic Reach National 
Policy Influence Type Participation in advisory committee
Impact I participate in the MRC Stem Cell Bank User's group and participate regularly in MRC stem cell policy and funding strategy meetings at Head Office.
 
Description MRC stem cells
Geographic Reach National 
Policy Influence Type Participation in advisory committee
Impact I participate in the MRC Stem Cell Bank User's group and participate regularly in MRC stem cell policy and funding strategy meetings at Head Office.
 
Description regular citations in clinical reviews and publications
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in other policy documents
Impact influence on development of NECTAR and ASNTR guidelines
 
Description CHDI contract grants
Amount £497,251 (GBP)
Organisation CHDI Foundation 
Sector Charity/Non Profit
Country United States
Start 01/2008 
End 12/2009
 
Description MRC Project Grant
Amount £1,340,940 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2008 
End 02/2010
 
Description NEUROSTEMCELL European Consortium for Stem Cell Therapy in Neurodegenerative Diseases (12m euros across 16 participants)
Amount £1,728,580 (GBP)
Funding ID 222943 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 12/2008 
End 11/2012
 
Description PDS project grants
Amount £310,115 (GBP)
Organisation Parkinson's UK 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2007 
End 08/2008
 
Description STEMSTROKE Towards a stem cell therapy for stroke (2.5m euros across 6 participants)
Amount £262,342 (GBP)
Funding ID 37526 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 01/2007 
End 12/2009
 
Description Welsh Office of Research and Development (WORD)
Amount £249,934 (GBP)
Organisation Health and Care Research Wales 
Sector Public
Country United Kingdom
Start 03/2009 
End 03/2012
 
Title mTOPs 
Description Validation of alternative protocols for consented collection of human fetal tissue 
Type Of Material Improvements to research infrastructure 
Year Produced 2009 
Provided To Others? Yes  
Impact Resolves the outstanding block on limited tissue availability to allow multiple international research and clinical trials to resume. 
 
Description EU FP6 StemStroke 
Organisation Lund University
Country Sweden 
Sector Academic/University 
PI Contribution Development of behavioural analysis and functional assessment of neural grafts in animal models of striatal stroke.
Collaborator Contribution Development of MCAO lesion model and stem cell transplantation and behavioural analysistraining in MCAO models and collaboration in cell grafting, imaging technology and behaviour
Impact Development of new method of MCAO occlusion with improved animal welfare Characterisation of motor and cognitive deficits after unilateral striatal stroke Evaluation of efficacy of primary striatal cell transplantation in stoke models. Publications pending
Start Year 2007
 
Description EU FP6 StemStroke 
Organisation Max Planck Society
Department Max Planck Institute for Neurological Research
Country Germany 
Sector Academic/University 
PI Contribution Development of behavioural analysis and functional assessment of neural grafts in animal models of striatal stroke.
Collaborator Contribution Development of MCAO lesion model and stem cell transplantation and behavioural analysistraining in MCAO models and collaboration in cell grafting, imaging technology and behaviour
Impact Development of new method of MCAO occlusion with improved animal welfare Characterisation of motor and cognitive deficits after unilateral striatal stroke Evaluation of efficacy of primary striatal cell transplantation in stoke models. Publications pending
Start Year 2007
 
Description 10-15 presentations to HDA and PDS patient groups 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Participants in your research and patient groups
Results and Impact 10-15 presentations to HDA and PDS patient groups. I present regular medical and lay seminars around the country and internationally. I am afraid I am unable to list all the individual presentations.

academic, medical and patient contacts
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description 10-15 presentations to HDA and PDS patient groups. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact I present regular medical and lay seminars around the country and internationally. I am afraid I am unable to list all the individual presentations.

various
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description 10-15 presentations to HDA and PDS patient groups. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact I present regular medical and lay seminars around the country and internationally. I am afraid I am unable to list all the individual presentations.

various
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description 10-15 presentations to HDA and PDS patient groups. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Participants in your research and patient groups
Results and Impact 10-15 presentations to HDA and PDS patient groups. I present regular medical and lay seminars around the country and internationally. I am afraid I am unable to list all the individual presentations.

various
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description results included in multiple public and academic lectures and seminars 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact results included in multiple public and academic lectures and seminars

various
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description results included in multiple public and academic lectures and seminars 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact results included in multiple public and academic lectures and seminars

various
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010