Improving the patient journey for those suffering from neurological disorders

Quicker diagnoses and better treatments for the approximately 800,000 people affected by neurological disorders in Ireland are among the key objectives of FutureNeuro, the SFI Research Centre for Chronic and Rare Neurological Diseases hosted at the Royal College of Surgeons in Ireland (RCSI).

Established in 2017 following a call from Science Foundation Ireland for proposals for new research centres, FutureNeuro projects aim to bring diagnostic supports to market, a pipeline of new drugs, and connected health solutions that enable patients to monitor and report their health better than before.

"We started out with a core group comprised of a mix of people doing neuroscience research in universities who were working with neurologists and clinicians," says FutureNeuro director David Henshall. "We saw an opportunity to create a centre focused on addressing huge challenges presented by rare neurological diseases. The concept was to establish a centre with patients and neurologists at the centre and aimed at developing solutions for their needs."

Extremely challenging

The centre focuses mainly on the three research themes of diagnosis, therapy and e-health.

“Diagnosing epilepsy can be extremely challenging, for example,” Henshall notes. “The key characterisation is having a seizure, but they come out of the blue and not very often in most patients. A clinician is very unlikely to see a seizure. Diagnosis involves talking to the patient about their history and so on. You might be able to use technology like an EEG, but some patients can have normal-looking EEGs.”

This is being addressed by bringing genetics and genomics into the diagnostic process. “We want to give neurologists access to genetic information to support diagnosis. We are also looking for other molecules in the blood and biofluids that will support a diagnosis. Our research has shown that there are a number of molecules produced in the brain that are associated with epilepsy and we are looking for ways to test for them.”

Therapy is equally if not even more challenging. “It’s very obvious that we don’t have good treatment for many or even most brain diseases,” Henshall explains. “Epilepsy has some good drugs, but they don’t actually treat the underlying condition. They dampen down the brain’s excitability and they can have side effects like lethargy and so on. We are committed to finding disease-modifying therapies.”

He compares the brain to a complex network of wires with a fault in one of its pathways which causes occasional sparks which can trigger seizures. “Can we fix the fault?” Henshall asks.

Another area of focus is motor neurone disease or ALS (Amyotrophic Lateral Sclerosis). “The situation for patients is so dire, there is literally no treatment,” he says. “We are looking at the mechanisms that regulate brain function and the switches that control gene activity. If we can switch on and off the genes involved in the disease, we might find a therapy.”

The e-health research theme encompasses all areas of how people have their conditions treated, monitored and managed. “The electronic health record is potentially a very useful source of research data,” Henshall says. “It you apply AI and machine learning to crunch through the huge amounts of data in the record you might find something that predicts someone’s disease curve. The big challenge is doing it in a responsible and safe way. Safe management of patient data is one of our areas of expertise.”

E-health also includes wearables and the way patients will be looked after in the future. “Some clinicians have been pioneering remote consultations for the past couple of years,” he says. “Now with Covid-19 that’s been very good for some patients.”

Breakthroughs

The centre has already made a number of significant breakthroughs. One was the discovery of increased levels of a certain group of molecules in the blood of patients before they have seizures. “At the time we were looking for molecules that might be associated with epilepsy and measuring their levels before and after a seizure.

“An unexpected finding was that these molecules had higher levels before a seizure. We think we may have found a predictive biomarker. This is fantastically exciting. Ultimately, we might develop a device to predict seizures like a glucose monitor like a diabetes patient.”

Another breakthrough was the development of new ways to study motor neurone disease. "This is a collaboration with NUI Galway where Prof Sanbing Shen has developed processes to convert skin cells into brain cells. If you put the right chemicals into cells it can reprogramme them first into basic stem cells and then into brain cells. We can convert cells into motor neurones and study them to understand the disease and look for new mechanisms for treatment."

The guiding principle behind these discoveries is the desire to make a real difference for patients. “We want to make a meaningful change to the patient journey by speeding up diagnosis and getting better treatments to people, that’s the whole purpose of the centre,” Henshall says.