Webinar: Sharing Childhood Dementia Data and Patient Samples to Accelerate Research
This webinar was held on Wednesday 13 November 2024. It explored approaches to accelerate childhood dementia research through the sharing of patient samples and data. A distinguished panel of experts discussed the crucial role of patient samples, brain banks, and virtual registries to advance research.
Background
There is currently no centralised infrastructure for storing and sharing childhood dementia patient data and samples for research. Historically, research has been focused on one childhood dementia disorder at a time, and there have been few avenues for collaboration.
When families donate their children’s samples to research, they tell us they don’t want them sitting in one laboratory’s freezer, but shared and used to progress research as widely as possible. This webinar and panel discussion focused on working towards solutions that will enable greater collaboration among researchers to rapidly advance our understanding and treatment of childhood dementia.
Speakers:
- Dr Kris Elvidge (Chair), is Head of Research at Childhood Dementia Initiative. Kris has more than 20 years experience in the medical research field, over 8 of those in the childhood dementia sphere. Kristina’s expertise lies in gathering evidence and galvanising stakeholders to accelerate the development of much needed treatments.
- Associate Professor Markus J. Hofer has more than 20 years of experience as a clinical neuropathologist and researcher. He is the consultant neuropathologist for the New South Wales Tissue Resource Centre and deputy chair of the brain and body node at the Charles Perkins Centre, University of Sydney. Patient samples have been pivotal to Markus’ research to understand a type of childhood dementia called Aicardi-Goutières syndrome, research which has recently led to the development of a potential therapy.
- Associate Professor Greg Sutherland is research group leader in neuropathology, Director of the NSW Brain Tissue Resource Centre (brain bank) and A/Prof in Neuroscience in the School of Medical Sciences, based in the Charles Perkins Centre, University of Sydney. Greg is spearheading an international virtual rare disease brain bank initiative to enable the sharing of brain tissue for paediatric brain disorder research.
- Dr Laszlo Irinyi, PhD, is a Senior Project Officer at NSW Health Pathology. He works on a project funded by the Office for Health and Medical Research to create virtual registries for cell and gene therapies as well as childhood dementia.
Summary
The webinar started with three presentations:
- Associate Professor Markus J. Hofer (University of Sydney) discussed his research into Aicardi-Goutières syndrome (AGS), emphasising the importance of collaboration and the challenges in accessing patient samples.
- Associate Professor Greg Sutherland, Director of the NSW Brain Tissue Resource Centre (brain bank) presented an initiative called Brain Bank Connect, a virtual international registry aimed at connecting brain banks worldwide to facilitate rare disease research.
- Dr Laszlo Irinyi discussed examples of successful biobank networks and the potential for a similar approach in childhood dementia research.
The speakers highlighted how current brain and biosample banking systems are fragmented and ineffective for rare childhood diseases, and emphasised the need for better collaboration between researchers, clinicians, and patient advocacy groups.
The panel discussion featured Jo Kershaw highlighting families' prioritisation of research, Greg discussing brain tissue banking, and Professor Jennifer Byrne addressing biobanking strategies.
Key challenges discussed included informed consent, ethics, funding, and data standardisation, with emphasis on implementing “FAIR" principles for data sharing.
Questions and Answers
Do you think the difficulties faced with brain banks around national/global linkage, consistency, access to samples etc are unique to brain samples, or does this extend to other tissue banks for rare disease?
Some patient samples are available from large biobanks such as the Coriell Institute for Medical Research and from disease-specific collections for example, the The Newcastle Mitochondrial Research Biobank. There isn’t a global database to link all the samples or improve consistency, and this would be a much larger proposition with many different sample types. In general, similar issues apply.
Biobanking blood has some of its own complexities: it has many different derivatives based on local protocols, so the complexity of the database would be increased. Some assays require special and time-sensitive handling so not all samples would be useful for a particular research project. There is likely to be the same restrictions on sending blood between countries – these relate both to personal data but also that genetic information can be extracted, etc.
Eyes are also part of the central nervous system, and from my research experience, they are relatively easier to access compared to brain tissue through existing eye donation programs both in Australia and internationally. However, they are often overlooked by researchers.
Markus Hofer said: I agree that they are often overlooked. Also, while they are part of the CNS, there are clear distinctions between the eyes and brain (e.g. in relation to the blood-brain barrier and cell types present). In regard to AGS, to my knowledge, eye pathology is not a key symptom that has been reported. We have also looked at the eyes in our mice with brain-targeted overexpression of interferon-alpha and could not find any overt abnormalities.
Greg Sutherland said: From a brain bank point of view, we rely on in-kind cooperation of mortuaries and their staff, so any procedure needs to be as quick as possible. Therefore, collecting multiple tissues has not been on our radar. Having said that, the Organ Donor Tissue Service does collect many tissues from their donors and it might be possible, going forward, to work more closely with them (indeed, we have had preliminary meetings to this effect).
For Greg. Whilst we wait for all this incredible work to come together, how can we respond to families now? Do you have any advice for how families can drive banking of brain tissue should they wish to?
Answered live: Greg Sutherland said: As discussed, my team and I are really happy to help any families with this process. My bank can only collect for diseases where we have ethical approval and funding, but we can act as a conduit to move tissue to bonafide researchers or banks with larger collections. This was one of the major reasons for setting up the Brain Bank Connect (BBC), so that banks worldwide can work together more closely. It is possible that an Australian bank could be the home for one such collection, and I am happy to work with patient organisations and researchers to see if there is a demand.
Do we need to make a rare disease biobank, or would it be better to have larger biobanks that serve multiple functions/research aims in order to utilise the same storage/infrastructure costs (lots of smaller biobanks increase the cost to manage)?
Markus Hofer said: Initially, it would be best to rely on existing expertise and infrastructure. However, it would be good to try and implement uniform guidelines on tissue processing and storage. Ultimately, the most efficient way would be to co-localise tissue for specific diseases. However, due to local laws and restrictions, this may not be possible.
Greg Sutherland said: Yes, this is a good idea and one that I have also proposed recently. The best brain tissue samples are those with lots of clinical data. For the brain, this will typically mean imaging, but also, there is an increasing improvement in blood-based markers. After their death brain tissue can be directly compared to the person's clinical pattern – this direct clinicopathologic correlation is a very powerful approach for finding new diagnostic markers and therapeutic targets. It does, however, require more interoperability between banks/health providers and this has been hard to date. A single identifier (as discussed in the webinar) would be a great start, so AI could be used to bring data from multiple sources together and analyse it.For hereditary conditions, what late-life effects have been researched for mothers [and fathers]?
Relatively recently, it was discovered that carriers of some childhood dementia gene mutations (previously thought to be asymptomatic), have an increased risk of developing dementia and/or Parkinson's disease later in life (e.g.GBA, MCOLN1 and SMPD1 genes) (Clark et al., 2015). This further cements the link between childhood and adult-onset dementia, but there is more work to be done in this area, which could be leveraged for the development of therapies that could work both for the childhood-onset rare disease and more common adult-onset neurodegenerative conditions.
Are there any restrictions/what are the criteria for banking a brain in Australia? Just also want to highlight the importance of considering rare disease coding in BrainBankConnect, not only a disease name.
Restrictions relate to clearance of infectious diseases, but then there are more subtle impediments like facilities for tissue retrieval and staff who can assist, for what is likely to be a very sporadic requirement. Any disease would need to be incorporated into ethics, while childhood diseases raise extra complications around type of consent and potentially re-consenting (and also ability to consent). All of this is likely doable, but would require dedicated admin support.
Yes, rare disease coding (e.g. ORPHACodes) is very important for any rare disease data and/or patient sample activities.
The benefits are obvious and the sector is obviously in agreement that it needs to happen. What are the barriers to making this work? I think there are a lot of lessons/opportunities from the international Brain Bank Connect example.
Markus said: Great question. There are two key issues that need to be resolved: (a) willingness of existing banks to share information (not tissues, just information); many of the brain banks Greg and I have been talking to are happy to participate BrainBankConnect (b) financial and technical resources to set up the online database.
Greg said: It's the classic NGO dilemma where there is such a need, and goodwill, but it needs resourcing. BrainBankConnect is trying to see what can be done with limited resources. Markus and I feel if we can build momentum, then formal funding channels can become available. Alternatively this might appeal to a Philanthropic organisation. On the positive side, the rare disease community and brain banking community are keen to get this project happening and we are happy to use existing resources to kick it off.
Poll results
