Autologous adult human mesenchymal stem cells: a neuroprotective therapy for multiple sclerosis

Lead Research Organisation: University of Cambridge
Department Name: Clinical Neurosciences

Abstract

MS is a disease where nerves and its insulation layer are damaged leading to symptoms. Over time the nerve damage accumulates leading to fixed and progressive disability in the vast majority of patients. Therapies for MS presently are limited only to partially reducing the frequency of individual attacks. There are no effective treatments to protect the nerves. This study is trying to explore whether stem cells taken from the patients bone marrow or skin could through a cell infusion (similar to blood transfusion) protect the nerves of the MS patient.

Technical Summary

Multiple sclerosis (MS) is the commonest cause of neurological disability in young adults. It is a cause of significant morbidity and mortality in the industrialised world with prevalence estimates ranging from 110-175 per 100 000 in the UK. It is a multifocal and multiphasic immune mediated disease characterised pathologically by inflammatory demyelination, axonal injury and partial remyelination. Therapeutic treatments of MS thus have two aims; to prevent (disease modifying) and to repair damage that has already occurred. Although some advances in treatment to reduce relapse rate have been made in the last decade, little has been achieved in terms of definitive treatments for relapse, prevention or repair of fixed disability and disease progression. The lack of such therapies represents a substantial gap in the treatment of MS. There is a need to develop treatments that prevent axonal loss, the primary correlate of clinical disability. This first into man proposal builds on our existing expertise on somatic adult stem cells, immune treatment of MS and non-invasive imaging markers of axonal loss and remyelination. A series of studies using animal models of MS have demonstrated neuroprotection following intravenous delivery of precursor cells. We propose to define an initial cohort of patients and using a cross-over trial design will examine the neuroprotective therapeutic potential of intravenously administered autologous adult human mesenchymal stem cells. Our approach is to identify prospectively cohorts with clinically articulate lesions involving the optic nerve in which detailed protocols can be subsequently evaluated for screening the outcome of a more widely distributed neuroprotective cellular therapy, extrapolating the experience of the sentinel lesion to the disease as a whole. The optic nerve is our favoured target given its clinical eloquence and the ready access to neurophysiological and serial quantitative imaging outcomes. This proposal addresses several areas highlighted by the grant call being a proof of concept study to examine the neuroprotective therapeutic potential of intravenously administered autologous adult human mesenchymal stem cells in MS.

Publications

10 25 50
 
Description Advised and chair Multiple Sclerosis Society Panel on a unified UK strategy on potential bone marrow transplantation therapies for MS
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description Evelyn Trust, Project Grant
Amount £125,000 (GBP)
Organisation The Evelyn Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2007 
End 06/2010
 
Description MRC iPS addendum
Amount £50,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2008 
End 11/2008
 
Description MS Society Project Grant
Amount £50,000 (GBP)
Organisation Multiple Sclerosis Society 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2010 
End 12/2010
 
Description MSC generation 
Organisation University of Cambridge
Department Department of Haematology
Country United Kingdom 
Sector Academic/University 
PI Contribution Patient sample derivation
Collaborator Contribution Hugely, understanding of principles of GMP for cell manufacture
Impact Multi-disciplinary. Research publications
Start Year 2006
 
Description Paolo Imperial 
Organisation Imperial College London
Department Department of Neurology
Country United Kingdom 
Sector Academic/University 
PI Contribution Trial design, protocol development, patient stratification
Collaborator Contribution Methods for patient selection, trial design, measuring neuroprotection
Impact Successfui award of grant MSS/SCF for trial to recruit 2012
Start Year 2010
 
Description Academic talks 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Academic presentations and workshops including MRC - British Council in Germany

Engagement - potential collaborations
Year(s) Of Engagement Activity 2008,2009
 
Description MS Society Forums 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Third sector organisations
Results and Impact Public lectures

Public engagement
Year(s) Of Engagement Activity 2009
 
Description Parliamentary visit 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Formal lobbying at Parliament as part of a MS Society sponsored delegation

Engagement, parliamentary question tabled
Year(s) Of Engagement Activity 2009
 
Description Patient AGMs 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Q & A, lots of discussion and follow up around patient participation in research, trials and ethics therein

As above
Year(s) Of Engagement Activity 2009,2010,2011
 
Description Public Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Open public lecture at Edinburgh attended by 250 people

Public engagement
Year(s) Of Engagement Activity 2009