Alexandra Petrache, valued member of HRW Synapse and HRW Shift, has long been interested in the potential to use brain stimulation to treat neurological conditions such as epilepsy. She recently interviewed Dr. Frances Hutchings, computational biology researcher at Newcastle University to see what the future holds in this space, and to hear about her own experience in care work with epilepsy patients. She also spoke with Kirsty Page, Director, who shared her experience living with juvenile myoclonic epilepsy and shed a light on what developments she is looking for as a patient in our most recent blog, ‘Epilepsy Neuromodulation’.


Would you try a device that would alter your brain’s activity?

Kirsty Page: It would depend on how invasive it was. If I had not responded to first-line therapy, and if there were no impact on my daily life, like a “one-shot” thing with monthly check-ups afterwards or so to make sure it is working then that would be fine, because one of the burdens of having epilepsy is just taking medication daily. I take 10 tablets a day to control it and having the opportunity to be free from that would be compelling.

Alexandra Petrache: Frances, do you think there is a place for such a device alongside pharmacological therapy?

Dr. Frances Hutchings: I think so. There are some people out there who do not respond to drugs at all, or people who respond only partially so they will have a reduction in seizures, but they still can happen. That is still significant because one of the hallmarks is often that it is very difficult to predict when a seizure is going to happen. You could potentially use a combination therapy to help bring someone to full seizure freedom.

Hopefully further down the line we can produce non-invasive stimulation treatment; one that we have been working on involves optogenetics (a combination of genetic engineering and light stimulation of selected neural targets) and that would involve brain surgery to have an implant and it does come with risks. But there are modalities out there being developed that can potentially be applied without any surgery, maybe in a few decades’ time. It would be a powerful tool because one of the benefits of a deep brain stimulation technique (DBS) compared to pharmaceutical techniques is that with drug treatment you affect the whole brain, whereas with the brain stimulation, if we know where in the brain something is going a bit wrong, we can target a specific area and that would reduce the risk of side effects.

KP: Luckily, I have never experienced any side effects [from taking tablets]. My doctor and I did not really talk about side effects because I needed to take the tablets anyway. I think if I if I were in the group who was not responding or was moving down lines of therapy, I would absolutely have more questions around side effects.


Do these advances progress at the same pace for all conditions?

Dr. Frances Hutchings: Right now, Parkinson’s disease seems to be the big one for DBS. In some patients it is very effective, the tremors go away when the device is switched on and it really can have a dramatic effect on patients’ quality of life, which it is a showcase of just how effective it can be. However, there is still so much that we don’t understand about what’s happening and what is going on with diseases of the brain such as epilepsy. You can monitor seizure activity, but we don’t really understand what is causing them to start in any given case. And if you can get to the bottom of that, then I think we will really be able to come up with a lot more individualised, effective treatments. There has been a lot of research recently into DBS for severe depression, and there do seem to be some promising results there. The crux for a lot of in most cases is knowing where to intervene specifically.

Hopefully, that’s somewhere where computer modelling can come in. A lot of the current treatments being trialled are open loop, so you just you have an electrode and it’s just giving a pulse every so often. That is how a lot of DBS for Parkinson’s works, and it seems to be surprisingly effective. But there is a bit of guesswork involved in what timing to use for that and if we can get better at monitoring on an individual case, then we can hopefully fine tune these things a lot more to be much more effective both for cases where it is working and for those where it isn’t- the reason for it not working might just be down to the wrong parameters.

Kirsty Page: Frances, are you thinking about it in relation to post-surgery use, or would it be pre surgery as well?

Dr. Frances Hutchings: It would depend on the individual person, on where the focus for the seizures is likely to be, because there are some areas of the brain that you really do not want to alter and damage- the language areas, for example, or memory. But there are other parts where the side effects from surgery have been surprisingly minimal, and a lot of that has been found out from epilepsy surgery. So, for certain types of epilepsy, surgery is reasonably tried and tested, and, in many cases, it can be quite effective and with minimal side effects, but if you do not have a type of epilepsy where that is established to be the case, then I think brain stimulation could be useful further down the line once techniques have been refined. The question is- is this something worth trying before surgery? Because DBS is a very experimental therapy, surgery is just more established.


Where do you think neuromodulation will be in let’s say 10 years? What do you hope it will have achieved by then?

Dr. Frances Hutchings: A lot of it hinges on better understanding of the underlying pathways involved in the disorders that you are trying to treat, even more so than neuromodulation techniques because in some ways we have the technology, for example, for making stimulation electrodes. The modulation is not the hardest part, the hardest part is finding a target for it to be effective and identifying the right treatment parameters. There is a lot of scientific progress going on to try and understand the biology underlying all the disorders we have talked about, whether they are mental illnesses or anything like Parkinson’s or epilepsy. So, I am hopeful that in 10 years’ time we will be able to sit here and say, “well, we have a much better understanding of what’s actually going on in the brain”. And from a clinician’s point of view, they can say, “for your specific case, this is a treatment that we can recommend”- whether that’s targeted pharmaceutical therapy or neuromodulation.


If you were to give pharma companies operating in the epilepsy space some advice, what would that be?

Kirsty Page: The ideal treatment for me would be something that would take the tablet burden off me to reduce the focus being drawn to my epilepsy- I am reminded of my epilepsy twice a day. I would like a treatment to give me some hope and some control, maybe something long acting. It should be an avenue that is explored as soon as possible because I think the drugs currently available are quite old.

Dr. Frances Hutchings: I have not heard much about any new therapies being developed for a long time. There is still a significant number of people who have either drug resistant epilepsy or only partially controlled epilepsy. And as we have discussed, that has a significant impact on lives and to have a group of people who are just falling by the wayside without treatment is a real problem. And I hope that we can develop new alternative therapies and focus on DBS and other treatments out there that have not yet been explored.


By Alexandra Petrache

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