Focus on research: Prof David Henshall, FutureNeuro

David Henshall, FutureNeuro
David Henshall, FutureNeuro

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6 November 2017 | 0

David Henshall is centre director of FutureNeuro, one of four Science Foundation Ireland research centes launched earlier this year. In this interview he discusses the centre’s focus on epilepsy research and how genetic information could become part of your regular hospital record.

Tell us about your academic background
My background is in pharmacology, which is the study of drugs and how they affect the body. I did that at the University of Edinburgh after doing an undergraduate degree in Bristol. I then went to the US and did six years working in Pittsburgh and Portland, Oregon. During that time I developed an interest in epilepsy research and trying to understand the mechanisms and treatment.

I moved to RCSI in 2004 as a senior lecturer, I’m a full professor here now in the Physiology department.

What is the concept of FutureNeuro?
The centre has three thematic areas: diagnosis, therapy and connected e-health. My own lab focusses on epilepsy but there are other neurological diseases which the centre will be interested in, like motor neuron disease.

In terms of epilepsy, diagnosis can be problematic. Are we seeing new tools and techniques emerge in this area?
On diagnosis, the big change is around genetic testing. The current way to diagnose epilepsy is by taking a long patient history and doing a clinical examination, like an EEG recording or a brain scan. We also know that a patient’s genetic background has a strong influence.

What will be happening in the next few years is that in addition to having those diagnostic tests you can give a blood sample and a genetic screen of a patient’s entire genome can be done to look for mutations that could be causing epilepsy.

If you’re ‘lucky’, you’ll come across a mutation where there is a specific drug known to be effective. We need some other things to happen at the same time for that to work. We need more of a digitised healthcare system linking genetic information to hospital records.

Research is changing all the time and there are mutations that we have no idea if they have anything to do with epilepsy. Everyone has some kind of mutation, a few errors in their genome, we just don’t know yet which ones are important for our work. It might be that in five years time someone discovers a particular gene can cause epilepsy, then doctors can review their patients’ digital records and see if they have this mutation and contact them about an ongoing clinical trial that might be helpful.

This is part of the grand vision. It will take a while to get there but that’s where we hope things are heading.

This is a massive project. How has the uptake been so far?
Already, there are about 10,000 patients in Ireland on the electronic epilepsy patient record. Patients are really embracing this and are on board with how this can change their care.

The electronic health record for epilepsy has been called a ‘lighthouse project’ by the HSE for e-health in Ireland. They’ve supported a lot of research into what the needs are for the patient and the clinician with regard to data protection and informed consent and these kind of issues are being tackled.

You mentioned industry partners. Who are you looking to work with?
We’re hoping to have industry partners linked to the three thematic areas of the centre and at the moment we have companies linked to each of those.

One company we’re working with is interested in getting genetic diagnosis into clinical practice, basically providing software and tools so a clinician can easily understand complex genetic data.

In putting the centre together you must have been looking at a broad range of research interests. What kind of backgrounds are people coming from?
There are a number of principal investigators linked to the centre. There are three what you would call traditional neuroscientists, two clinicians who are neurologists caring for patients with a number of neurological diseases, and we have other scientists which have complimentary strengths.

For example, Matthew Campbell at Trinity College Dublin is interested in the ways to get drugs into the brain.

We’ve also got Robert Forster, a chemist based at DCU who is developing ways to detect some of these new diagnostic molecules that we know appear in the blood. We think they may be coming directly from the brain. What he’s trying to develop is a rapid detector of these types of molecules. At the moment detection may take hours and hours or even a couple of days in a lab to go from taking a sample to getting a result.

Lastly we have a cell biologist, Sanbing Shen, based at NUI Galway. He has developed a technology to take skin cells from patients and turn them into brain cells, that way you can look at how these brain cells perform relative to a normal cell. You might get some inkling as to why that patient has a hyper-excitable brain. You can also screen these cells with drugs. You could take a catalogue – not just of available treatments for that one disease, but any treatment that has been approved for any disease and see if it works. This has actually been done for one of these rare childhood epilepsies called Dravet Syndrome which has been quite successful where they created a cell model and screened everything and it turned out there was a drug being used for depression which seemed to stop the hyperexcitable response. There are now clinical trials where this is being done.

Being able to recreate brain cells from skin cells does raise an ethical question. Developing a few cells in a lab is one thing but how far is too far in progressing a technology to the stage where you have the capacity to replicate entire brains?
That’s a good point because the technology has moved beyond simply culturing a mono-layer of cells where they perform very simple rudimentary network connections. You wouldn’t ever consider there to be an ethical issue there. But we are moving towards what we call ‘cerebral organoids’ where you can culture these cells to grow and they do seem to develop rudimentary brain shape.

So far there’s not enough research to know whether one of these cerebral organoids – which are microscopic really (little dots in a dish) – if there is enough spontaneous connective activity to consider it as something that could be sentient or conscious.

My feeling is this isn’t going to be an issue. That either the degree of connectivity is not sufficient to create what we might call ‘consciousness’ or ‘sentience’.

I think if the technology develops to the point that these become more complex until they become true ‘mini brains’ we are going to have to think carefully about ethical issues around how those cells are treated and destroyed. I think we’re a few years away from needing to consider that but we need to be ready for it because the ethical landscape will change as the technology changes.

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