Being Patient meets John Gallacher, Professor of Cognitive Health at Oxford University and Director of the Dementias Platform UK (DPUK), to find out how this network of 300 scientists is transforming Alzheimer’s research in Britain. Scientists working with the platform are now sharing data from more than two million study volunteers. Through its focus on human trials, rather than the experiments on mice, the platform is hoping to speed up the process of developing new treatment approaches.
- Scientists are using existing data to identify genetically predisposed community of ApoE4 carriers
- DPUK is collaborating with an Oxford research group to find biomarkers of Alzheimer’s disease
- Research still at the stage of focusing on mechanisms of Alzheimer’s more than treatments
Being Patient: Why is it so difficult to identify a specific cause and treatment for Alzheimer’s disease?
John Gallacher: I think it’s because it’s not a single disease. For a very small proportion of individuals there is a strong genetic link but for the rest of us, what you have is effectively the incremental impact of a number of small processes which eventually add up to dementia. That is the problem. What we would call dementia is the end point of several pathological processes. So, even though you might think “oh, my memory is going”, that’s probably for three or four different reasons. They could be vascular reasons or it might be that you have an up-regulated inflammatory process going on in your body. Until we can get a better handle on what the actual disease processes are, then it’s very hard to actually treat them.
Being Patient: Alzheimer’s dementia is defined by the presence of beta-amyloid plaques and tau tangles. Do scientists understand how they contribute to the breakdown of brain cells (neurons)?
John Gallacher: The current thinking is that amyloid triggers tau and then tau triggers more amyloid. Then tau spreads the amyloid-triggering process to other neurons. That gives you three or four different opportunities to intervene and those might be different depending on the person. Until we can work out exactly how to target therapies to specific individual requirements, it’s going to be really difficult to have very efficient drugs.
Being Patient: Dementias Platform UK is bringing together data from 30 cohort studies taking place in Britain. How does pooling so much data help you to develop approaches that are specific to an individual’s needs?
John Gallacher: In the UK biobank study we have 500,000 people and we have genetics on all of them. Within those 500,000 we have something like 17,000 who have poor memory scores. Within those 17,000 we have 12,000 who are over the age of 55. Within those people who have poor memory scores, over the age of 55, we have roughly two-and-a-half-thousand who are genetically at risk, carrying the ApoE4 gene.
Those two-and-a-half-thousand are really interesting [participants for clinical trials]. So rather than having a big ad in the newspaper that has no chance of identifying these really informative individuals, I can do that within five minutes on my computer because I know what I’m looking for and the data exists. That doesn’t mean to say there aren’t issues with how you approach these individuals. There are very serious ethical issues which we are currently discussing. They don’t know they’re carriers of the ApoE4 gene because they just volunteered to be part of this biobank.
Being Patient: How will taking a collaborative approach help in the search for a cure?
John Gallacher: All of the clinical drug trials have failed. We’ve had no treatments coming to market for 13 years. In truth, we’re not much closer to a treatment now. There has to be a different way of doing this. Taking a collaborative approach de-risks the environment [for researchers] by bringing the best minds together, getting the best ideas and only doing the best science. We want to de-risk doing trials so that when we recruit person X into trial Y we know they are the right person for this trial.
We have a network of roughly 300 scientists and have generated over $12 million pounds (GBP) of grant funding in the last 12 months. I think the best is yet to come, if I’m honest with you. Dementia research is not known for collaboration and once people begin to believe in the concept, it just increases in momentum.
Being Patient: What are some of the trials you’re currently conducting?
John Gallacher: We’re working with Simon Lovestone at Oxford University on the Deep and Frequent Phenotyping study. Now the DFP study is not a trial in the sense that you are giving somebody an active agent. It’s very intensively measuring and remeasuring [potential biomarkers for the disease] so we can identify what changes over time. We’re hoping to identify which biomarkers change most quickly. If I have a biomarker which is really plummeting or increasing, then that’s very informative. And if I can identify what those biomarkers are, if they exist, we would then use those biomarkers to select people for participation in trials.
Being Patient: What do you think are the most exciting ideas for a new directions in research?
John Gallacher: We’re way off treatment so we are still looking at mechanisms. Bringing together inflammatory processes and vascular processes into the normal amyloid tau cascade is really exciting. So we’re not talking about the neuro units, we’re talking about neuro-vascular units [the neurons and the blood vessels that supply them]. It’s this whole thing which is going wrong in a multitude of ways, so we need to study the whole thing to see which element is affecting the others and vice versa.