Project: Transcranial direct current Stimulation for Focal Refractory epilepsy in Mitochondrial disease (TRANSFORM)
Based at: Wellcome Centre for Mitochondrial Research, Newcastle
Research Leads: Dr Albert Lim, Prof Robert McFarland
In a nutshell, what is the idea behind TRANSFORM?
TRANSFORM is potentially a way to treat epilepsy in children and young adults with mitochondrial disease that does not involve medication or hospitalisation. Epileptic seizures are a prominent and debilitating symptom of POLG, one of the most common forms of mitochondrial disease. These seizures often manifest as epilepsia partialis continua (EPC), which is when the seizures are ongoing and very difficult to control. Currently the only way to manage the seizures is with multiple medications, each of which may have unpleasant side effects, or in severe cases to admit the patient to intensive care for general anaesthesia with all the complications that entails. There is therefore a real need for an alternative treatment.
How does treatment it work?
Seizures are the result of abnormal electrical activity in the brain. Essentially this device is placed on the scalp and delivers a very small electric current – equivalent to a regular battery that you might have at home – which calms the electrical activity causing the seizures. So far it's been tested in non-mitochondrial disease patients and the results have been positive; in some cases it's appeared to reduce or even eliminate the seizure activity. However the results are not yet conclusive, as they have yet to be proven in a controlled study using a larger patient cohort.
What stage is the project at now?
The concept has been approved by our ethics committee, so the next stage is to design an effective trial and recruit patients to be involved in it. The COVID pandemic has obviously impacted the project timeline, as patient trials have had to be put on hold. Now, we are trying to start it up again by finding ways to conduct trials safely in people's homes. One possibility is to work with the private sector to design a TRANSFORM device for home use. Vulnerable patients could be treated at home while they are shielding, and not have to travel. So it's about finding ways to future-proof this treatment, and make it as accessible to as many people as possible.
TRANSFORM is something that is very close to our hearts and we would like to explore this as a treatment for one of the most significant symptoms in children and young adults. Lily has very kindly provided the funding for this project, and we are very grateful for that confidence in our concept.
What evidence is there that the treatment can work?
We've already offered the treatment to a small number of patients on a compassionate basis, and it's shown good results. However, we need to eliminate the possibility that what we're seeing is a placebo effect. So our aim is to conduct a randomised, blinded trial using a working device and a dummy device that is basically switched off. This will determine if the results we've got so far are true. So we are conducting this study properly, using a rigorous scientific method, to see if what we are doing actually helps the patient.
What is the background of the research?
This research came from Dr Mark Baker, one of our consultant neurophysiologists here at Newcastle. He's spent many years researching direct current stimulation as a way to treat for other conditions, and there was already a lot of literature published that formed the basis for our research. We started from scratch, adapting the approach, and in 2015 we designed a prototype device. That was shown to be effective, and those results were published in 2018. Since then we have used it in more patients, and the results have continued to be positive – but the placebo effect has yet to be ruled out.
What are your hopes for the study?
Our hope is that patient trials will show the device significantly reduces, or even completely stops, seizures. If so, it will be a very useful intervention, and add to our arsenal of treatments that we can provide for mitochondrial disease patients. The patients who have tested TRANSFORM so far have had no side effects, and report improved results. This gives us hope that one day this will be a mainstream treatment for mitochondrial disease patients with epilepsy, and even expanded to help manage epilepsy in other conditions too.
How has The Lily Foundation contributed to this research?
The funding provided by The Lily Foundation has helped make this research possible, so we are extremely grateful for their confidence in our concept. In addition to providing funding, we have worked with Lily and MitoCohort(UK) to engage with patients and the public on how we can fine-tune the recruitment and trial process. By bringing in the patient voice at all stages of the study, we can design the trial in a way that is safe, informative and comfortable, and that really addresses the specific needs of the people it's designed to help. This sort of collaboration is vital to make the project as effective as possible.
When might this treatment be available to patients?
It's very difficult to put a timeline on things, but it is likely to be a few years yet before we have a device that clinicians can use in their practice. The limiting factor has been trying to recruit patients and safely conduct a trial during the COVID-19 pandemic, given the need for social distancing and the limitations of the space that we have. So it is challenging, but we still have a lot of confidence that we can move forward. There are not many treatments available for patients with mitochondrial epilepsy, so it's a very exciting project, and one that we are determined to see through to the end.
Study note:
The study is now open to people with mitochondrial disease and drug-resistant focal epilepsy who show anatomically relevant changes in the brain (neuroimaging or EEG).
If you are interested in finding out more, or would like to participate, please click here or contact us:
Prof Robert McFarland at +44 191 2825225, Dr Albert Lim via [email protected] or Katrin Bangel via