Presentation on theme: "2. Post mortem and tissue harvesting a) Post mortem delays Ideally, we seek to minimise the post mortem delay to less than 24 hours, where possible. We."— Presentation transcript:
2. Post mortem and tissue harvesting a) Post mortem delays Ideally, we seek to minimise the post mortem delay to less than 24 hours, where possible. We accept donations with post mortem delay (time between death and obtaining tissue for freezing and fixation) of up to 72 hours. This is to accommodate deaths that occur over a week-end or Bank holidays, when normally mortuary services are unavailable. b) Post mortem examination Whenever possible, neuropathologists would carry out complete full body or limited brain only post mortem examination soon after death. In a few cases, the post mortem examination is performed elsewhere by other pathologists if we anticipate delay in transferring the cadaver or for other logistic or social reasons. A previously circulated protocol becomes operational to ensure transfer of brain without trauma or delay. c) Brain tissue dissection and diagnosis Sets of standard protocols are in use for tissue sampling of fresh and formalin fixed material. The brain is divided along the midline in the sagittal plane: one half to be fixed, while the other is freshly sliced. The slices are coded according to their anatomical region and cortical broadman areas and stored in -80 C. The formalin fixed half of the brain would be examined by the team of senior neuropathologists to provide diagnosis according to a comprehensive protocol which is not only to satisfy reaching a correct diagnosis but also includes information about the load of the pathology staging and other information important for researchers. MRC London Brain Bank: a resource for research in neurodegeneration Claire Troakes and Safa Al-Sarraj MRC London Brain Bank, Institute of Psychiatry, London, UK ABSTRACT Clinically and neuropathologically well-characterised brain tissue is one of the most important resources for neurodegeneration research in the battle to develop new strategies and future treatments. There has been spectacular progress during the last two decades which has increased demand for high quality brain tissue from brain banks. The MRC Brain Bank at the Institute of Psychiatry was established in 1989 and has become a leader in the field of brain banking. The Brain Bank is a major source of high quality brain tissue, not only for research at the Institute of Psychiatry and elsewhere in the United Kingdom, but worldwide and has thus contributed to the success of many research programmes. The central aim of the MRC Brain Bank is to achieve gold standard in programmed brain donation, including regulated ad hoc donation, following best practice in ethical matters related to consent, donor family care, high standards of storage of brain tissue and easy access of tissue to researchers. We aim to focus our banking on neurodegenerative diseases, including Alzheimers disease, Motor Neurone Disease and movement disorders but also facilitate other smaller collections such as psychosis and autism in order to enhance research in these areas. The Brain Bank is a leading member of Brain Net Europe, a consortium of 19 European brain banks that are working towards standardisation and harmonisation of all aspects of brain banking, including neuropathological criteria, health and safety, ethical issues and many others. It also aims to pool tissue resources and data to a central on-line brain tissue repository to meet the needs of international neuroscience communities. The Brain Bank has also been appointed as central co-ordinating centre for a national network of brain banks to include, in addition to the Institute of Psychiatry, Newcastle, Oxford, Manchester and Cardiff. This organisation will be devoted to supporting research into Alzheimers disease and other categories of dementia. The MRC Brain Bank at the Institute of Psychiatry therefore serves as a vital conduit for the exchange and dissemination of best practice in brain tissue banking protocols within the United Kingdom and Europe, as well as providing a major resource for neuroscience researchers. Objectives of the MRC Brain Bank at the Institute of Psychiatry 1.Facilitate brain donation through an ethically approved programme of informed consent for cohort studies and ad-hoc donation. 2.Provide pathological diagnosis to the relatives of brain donors according to the best national and international protocols. 3.Dissemination of well preserved brain tissue for neuroscience research. 4.Maintain an open-door policy for responding to requestor without prejudice. 5.Ensure optimal donor care and retain contact with the brain donor families, informing them about diagnosis and progress in research. 6.Disseminate and promote knowledge of brain banking through scientific meetings, public engagements and newsletters. 7.Provide provisional teaching, training information and educational resources for neuroscientists. 8.Facilitate collaboration between basic research scientists, pathologists and clinicians. 9.Maintain gold standards of excellence in brain banking for the archiving and storage of frozen and formalin fixed tissue. 10.Participate in ethical training and consultation and implement the most recent ethical guidelines for donor recruitment through informed consent. A Year< 24 hs24-48 hs48-72 hs > 72 hs 200035%33%23%10% 200135%34%17%14% 200228% 20%23% 200340%38%14%8% 200434% 20%11% 200551%27%18%5% 200642%33%15%10% Neuropathological diagnosisStored material 1989 to 2006 Fixed Frozen TOTAL 1459 1228 EXAMPLES Alzheimers disease (AD) 420 335 AD-familial 32 13 AD & Cerebral Vascular Disease (CVD) 28 14 AD familial & CVD 2 0 AD & DLB 45 37 Autism 4 4 Cerebral vascular disease 65 41 Corticobasal degeneration 12 8 Prion disease (CJD) 26 39 Dementia with Lewy Bodies (DLB) 66 50 Downs syndrome 4 12 Frontotemporal dementia 40 31 Huntingtons Disease 10 8 Motor Neurone Disease 167 160 Multiple system atrophy 19 13 Non-specific neurodegeneration 25 20 Progressive supranuclear palsy 24 16 Normal brains 152 147 Brain tissue audit 1. Recruitment of cases a) Diseased brains Brain donations are accepted in the Brain bank via two routes: I. Donor programme: The majority of donations from Alzheimer disease, MND and movement disorders are registered through cohort studies. These donations are ideal and provide not only well-characterised brain tissue but a fully documented clinical profile, sometimes with neuro- imaging and neuro-psychological information as well. Such donations are very useful in many clinical molecular and genetic studies where knowledge of clinical and pathological heterogeneity is important; for example, familial Alzheimer disease and fronto-temporal dementia. II. Ad-hoc donation which has noticeably increased in the last few years. This is a very useful source of various types of dementias, other neurological conditions and normal control. b) Control brains - recruiting normal individuals in cohort studies; - liaising with the local transplant coordinating centres and Coroner; - expanding on ad-hoc donation. Disease categories requested2000200120022003200420052006Total 2000-06 TOTAL (formal tissue requests) Total no of requests Fixed samples Frozen samples Total samples (fixed and frozen) 101 1789 1889 3678 110 548 1054 1740 103 1427 1192 2619 35 2410 352 2762 25 2808 482 3290 41 3501 383 3884 26 241 242 483 441 12724 5494 18218 EXAMPLES Alzheimers disease (AD) Total no of requests Fixed Frozen Total (fixed and frozen) 27 363 182 545 32 139 340 479 27 125 329 457 10 3 255 258 5 0 274 12 8 190 198 11 44 19 63 113 638 1570 2211 Dementia with Lewy Bodies Total no of requests Fixed Frozen Total (fixed and frozen) 4 120 28 148 0 1 0 1 0 3 42 8 50 1 0 3 00000000 9 162 39 202 Fronto-temporal dementia Total no of requests Fixed Frozen Total (fixed and frozen) 7 26 18 44 2 0 25 5 29 7 36 0 1 0 4 1 0 16 5 19 45 64 16 55 70 125 Picks Disease Total no of requests Fixed Frozen Total (fixed and frozen) 5 9 15 24 3 42 18 60 2 0 18 1 0 8 0 1 0 4 00000000 12 51 59 114 Cerebral Vascular Disease Total no of requests Fixed Frozen Total (fixed and frozen) 0 2 15 30 0 2 0 19 00000000 4 15 34 49 Motor Neurone Disease (MND) Total no of requests Fixed Frozen Total (fixed and frozen) 5 48 34 82 9 72 63 135 9 590 53 643 2 60 4 64 4 1720 15 1735 4 2144 1 2145 5 60 38 98 33 4634 170 4804 Autism Total no of requests Fixed Frozen Total (fixed and frozen) 0 0 4 0 4 0 2 115 0 115 16061606 6 119 0 119 Normal brain tissue Total no of requests Fixed Frozen Total (fixed and frozen) 30 338 631 967 47 195 427 622 36 155 523 678 10 13 66 79 10 800 178 978 13 1232 99 1331 13 99 119 218 146 2733 1924 4655 Local Management committee Brain Bank Director IOP Manager Independent Steering committee Brain Bank Coordinator (full time) Support Kings NHS Trust Support Clinical Diagnosis: 1 MSLO II (full time) 3 Neuropathologists 1 Specialist Registrar Tissue Requests: Supported by MSLO II (part time) Administration: Supported by secretary (part time) IOP Brain Bank – Local Management 3. Tissue dissemination a) Open-door policy The MRC Brain Bank at the Institute of Psychiatry has a transparent and open-door policy providing services and brain tissue to requestors without prejudice, on condition that all ethical requirements are satisfied and that a scientifically sound case underlies the application. b) Requesting brain tissue The researchers are asked to complete a request application providing an abstract of the project, ethical approval, source of funding and other aspects. When the completed application request is received it is assessed by the Brain Bank Director. If there is any doubt regarding fulfilling the request because of ethical, scientific or other practical issues, the request is referred to the local management committee, who are empowered to make the final decision. c) History of tissue requested We have a wide range of national and international collaborations and are considered to be a major resource of brain tissue. We have responded to over 1,066 requestors for brain tissue since our establishment in 1989 with 457 completed requests between 2000 and 2006. In 2005, we have sent 3,884 samples (41 requests) compared with 1,602 samples (110 requests) in 2001. We distribute brains nationally and worldwide. Between 1989 and 2006, 595 samples were provided locally to the Institute of Psychiatry researchers, 387 to other London institutions, 419 to other UK universities, 64 to Europe, 15 to USA and 13 to the Middle East and Far East. 4. Donor care We have notable success in keeping in touch with families of brain donors, to inform them about the diagnosis and progress of research. The link of the Brain Bank with the future Alzheimers Brain Bank UK will allow us to improve upon existing procedures with a dedicated brain bank nurse. 5. Database information We currently have a database of donated brains and information on registered donors, detailing clinical and pathological diagnosis, post mortem details of fixed and frozen tissue and non-clinical data such as age, sex and source of donation. 6. Management There is involvement of lay people and representation from managers of clinical and non-clinical neuroscience for Kings College Hospital and the Institute of Psychiatry on the Brain Bank Management Committee. 7. Environment and links The Brain Bank at the Institute of Psychiatry has the following important links: MRC Centre of Neurodegeneration This is a newly established MRC Centre for Neurodegeneration at the Institute of Psychiatry with a mission to understand the mechanism of neurodegeneration and to translate this into new treatments, by carrying out translational research through new positions and equipment to facilitate interactions between the Centre and principal investigators in various groups. The Brain Bank occupies a central key role in this and is a critical resource for the execution of the Centre research. Brain Bank Net Europe The Brain Bank is a member of Brain Bank Net Europe which is a consortium of 19 other European brain banks. Brain Bank Net Europe aims to standardise laboratory procedure, diagnosis and promote teaching of research for brain banking in Europe. Alzheimer Brain Bank UK (ABB UK) The Brain Bank at the Institute of Psychiatry is an important component of a newly proposed Alzheimers Brain Bank UK which is funded jointly by the Alzheimers Research Trust and Alzheimers Society. The Institute of Psychiatry will act as the coordinating centre for ABB UK and will be a component Brain Bank along with Cardiff, Newcastle, Oxford and Manchester. The coordinating site will be responsible for: Creating and maintaining a web based database for all accessible samples in the component brain banks; Hosting training in organ retention, ethics and governance issues for ABB UK members; Introduction of a dedicated brain bank nurse who will be responsible for liaising with the donor and their families at the time of consent, at the time of donation and for a period afterwards, to offer support and information. Public Engagement The MRC London Brain Bank is committed to openness and transparency in its regulatory procedures and the research it supports. It regularly submits articles to patient support networks and newsletters and participates in public engagement exercises such as research Open Days Contact Details The MRC London Brain Bank practises an unbiased policy towards all peer-review tissue request applications however proof of local ethical research approval for the research project is required. Tissue request application forms can be requested from Brainbank@iop.kcl.ac.uk. Alternatively, please contact the Brain Bank Co-ordinator Dr Claire Troakes, ASB, 4 Windsor Walk, Institute of Psychiatry, London SE5 8AF. Claire.firstname.lastname@example.org. All applications are treated confidentially. Acknowledgement: We thank the Medical Research Council-UK for supporting the Brain Bank. We thank Mrs Mary Davitt, Dr Istvan Bodi and Dr Andrew King for advice and technical support.