The UK Multiple Sclerosis Tissue Bank - seven years on
Dr Abhi Vora, Manager
The UK Multiple Sclerosis Tissue Bank
Way Ahead 2005;9(1):6-7
Background
In 1998, the Multiple Sclerosis Society awarded a five-year grant to Imperial College London to enable the setting-up of a national Tissue Bank for research on multiple sclerosis (MS). The aim of this centralised facility, based at Charing Cross Hospital, is:
- to co-ordinate the collection of tissue donated for research into the cause and treatment of MS
- to distribute the donated material to scientists conducting this type of research.
The progress that the Tissue Bank had made over the first five-year grant period was assessed by an Independent Review Panel, appointed by the MS Society, that comprised of experts in neuropathology, neurology and research; and individuals affected by MS. Upon the recommendation of this Review Panel, the Society awarded a second five-year grant to the Tissue Bank. The overall conclusion reached by the Independent Review Panel was that the UK Multiple Sclerosis Tissue Bank was "one of the best Tissue Banks in the UK and Europe".
A facility for those wanting to donate tissue to research
An aspect of our work that has remained important throughout the seven years of operation has been the raising of our profile in the MS and healthcare communities. People affected by MS have come to learn of the importance of post-mortem human tissue to research through talks that we have given at branches of the MS Society and from articles in magazines published by the Society. The MS Trust has provided a number of means of raising the awareness of healthcare professions to our work - the Tissue Bank has featured in articles in Way Ahead and has been the subject of workshop and poster presentations at Trust Conferences. The value of our interaction with the Trust has been proven on a number of occasions when families of recently deceased, unregistered donors have given consent for the retrieval of tissues following discussions with MS nurses. These promotional exercises have resulted in our sending out over 4,100 information packs and registering 2,600 individuals on the Tissue Bank's prospective donor scheme. Figure 1 shows how the number of people requesting an information pack and registering as donors has continued to rise over the last seven years.
Since 1998, we have been in the privileged position of fulfilling the last wishes of 239 people who had lived with MS and 28 individuals who did not have the condition, all of whom wanted to donate their brain and spinal cord to MS research. Figure 2 shows the rate at which we have accrued tissue from these 267 donors over the last seven years. We have been overwhelmed by the willingness of a range of professionals who have helped us with the retrieval process, including: doctors, nurses, coroner's officers and pathology technicians; all working together to harvest the donated tissues with as little delay as possible. Their goodwill and the effectiveness of our collection procedure have allowed us to process tissue from 70% of our donors within 24 hours of death.
To date, we have concentrated on recruiting people living with MS onto our donor scheme, with the result that only 25% of the 2,600 registered donors do not have MS. Since research studies require tissue from patients that did not have MS in order to identify changes that are specific to the disease, we are now looking at ways of recruiting more people without MS onto our donor scheme. As a first step, we have collaborated with the MS Society to carry out a national survey to assess the general public's views on the donation of tissues, particularly the brain and spinal cord, to research. The results of this survey will allow us to develop a strategy to address the concerns that may be deterring individuals from registering on our scheme.
An essential resource for MS researchers
The second aspect of our overall aim - that of acting as a source of human tissue for MS research has also been successfully addressed over the last seven years. As a result of promoting the Tissue Bank as a resource for research, added to the high quality of service that we offer to researchers, the number of studies supported by the Tissue Bank has grown steadily over this time. We have supplied samples of tissue from 70% of all our donors to approximately 80 different projects. The pie chart on the left in Figure 3 shows that three quarters of these projects are being carried out in the UK. The studies cover the whole spectrum of research on multiple sclerosis, including:
- diagnosis
- earliest changes in normal appearing white matter
- proinflammatory cytokines and chemokines
- factors responsible for demyelination and axonal damage
- mechanisms of remyelination.
The pie chart on the right in Figure 3 shows how the 80 projects are distributed into these six categories. Examples of two projects that span this spectrum include the following:
Diagnosis
The Nuclear Magnetic Resonance Research Unit at Queen Square is studying a range of magnetic resonance imaging (MRI) techniques to find ones that will allow an examination of the different facets of the MS lesion. Brain slices from over 52 donors were scanned at the unit using a number of MRI techniques; lesions visualised in the images were sampled and examined microscopically for demyelination, remyelination and axonal loss. These features were then related to the MR images obtained of the whole brain slice. The aim of this project was to identify those imaging techniques that are best suited to studying the effect that MS therapies have on lesions in a person living with MS [1].
Remyelination
The process of myelination is inhibited during development by the expression of PSA-NCAM (polysIalylated-neural cell adhesion molecule) on the surface of axons; myelination proceeds only once this "non-stick" molecule has been down-regulated. To determine whether the re-expression of PSA-NCAM on demyelinated axons could explain the failure of remyelination in MS, a group working at the Hôpital de la Salpêtrière in Paris examined the presence of this molecule on myelinated, demyelinated and remyelinated axons in tissue samples from 24 MS donors and five control subjects. They found that PSANCAM was not expressed on myelinated axons in normal tissue from MS and control donors or on axons in completely remyelinated lesions. However, axons in completely demyelinated lesions were coated with PSA-NCAM, suggesting that the presence of PSA-NCAM prevents axons from being remyelinated in these lesions [2].
A facility and a resource for the future
In the first seven years of operation, we have become aware of the MS community's keen interest in the use of human tissue in MS research. The Tissue Bank serves as an effective facility to meet the needs of people who wish to donate their tissues to research. The Tissue Bank is already proving to be a valuable resource for research; we hope that the ready availability of well-characterised tissue samples will stimulate even more studies on this condition. Our aim for the future is to continue providing a service of the highest standard to both the MS and professional communities in order that the Tissue Bank may help achieve our shared goal of finding a cure for MS.
For more information contact:
The UK Multiple Sclerosis Tissue Bank
Division of Neuroscience and Mental Health
Imperial College London
Charing Cross Campus
Fulham Palace Road
London
W6 8RF
Telephone: 020 8846 7324
email: ukmstissuebank@imperial.ac.uk
Website: www.ukmstissuebank.imperial.ac.uk
References
- Schmierer K, et al.
Magnetization transfer ratio and myelin in postmortem multiple sclerosis brain.
Ann Neurol 2004; 56(3): 407-415. - Charles P, et al.
Re-expression of PSA-NCAM by demyelinated axons: an inhibitor or remyelination in multiple sclerosis?
Brain 2002; 125(9): 1972-1979.
