You need to know what FutureNeuro is doing with genomic sequencing

8 Jun 2018

RCSI, where FutureNeuro is based. Image: RCSI

Scientists from Ireland’s most esteemed universities have come together under RSCI’s roof to address the complex demands with treating neurological diseases, using the most cutting-edge technologies available.

Neurological diseases affect up to 1bn people worldwide, so the director of the Science Foundation Ireland (SFI) FutureNeuro research centre, Prof David Henshall, told me.

He continued: “According to the World Health Organisation, neurological diseases are the greatest challenge facing public health systems in developed countries worldwide. In Ireland, one in four people will be affected by a neurological disorder during their lifetime; the health cost of this is €3bn per year for the State.” 

As if their ubiquity wasn’t enough to make matters complicated, neurological diseases additionally tend to be both complex in the clinical challenges they present, and devastating in the effect they can have on the lives of patients.

Addressing all these factors and emerging with a workable solution is a Herculean task, one which requires a Herculean effort, such as the ones being made at FutureNeuro.

First established in 2017, SFI’s FutureNeuro is based at the Royal College of Surgeons in Ireland and it deals with chronic and rare neurological disease. It brings together researchers from RCSI, Trinity College Dublin, University College Dublin, NUI Galway and Dublin City University, supported by a clinical research network across Ireland.

It was born out of 10 years of collaborative research between scientists and clinicians to understand the roots of these diseases and translate this understanding into new, innovative therapies.

‘There is a large enough population for results to be relevant but a small number of clinicians to allow a national collaboration in identifying disease-linking biomarkers’

For many reasons, Ireland is an ideal location for such an endeavour. Irish scientists have a sterling international reputation in the area of neurological research, and the size of the Irish population offers an additional boon.

Henshall explained: “There is a large enough population for results to be relevant but a small number of clinicians to allow a national collaboration in identifying disease-linking biomarkers.”

For FutureNeuro in particular, significant scientific advances in genetics and genomic sequencing mean that the timing for the centre is optimal. Being able to better pinpoint the genetic causes of disease makes it easier to tailor treatments to patients, and the fact that the cost of genomic sequencing has nosedived considerably in the last few years means that this approach is becoming more and more accessible.

“The first human genome sequencing cost around €1bn in 2000,” said Henshall. “Today, it costs around €1,500 to sequence a human genome and this figure will continue to decrease to a point where having your genome sequenced costs less than an MRI scan.”

As it stands, there is very little that can be offered to patients with neurological diseases. There are very few effective treatments and sometimes none at all. Any medicines that are available to people are often hit-and-miss or have quite serious side effects that will further impact negatively on quality of life. So, the ability to interpret genetic information or detect a molecule in the blood that indicates disease risk would, as Henshall put it, “transform clinical practice”.

Startling insights from genomic sequencing

It is this dream of transformation that drives the research at FutureNeuro, so explained Prof Gianpiero Cavalleri, a professor of human genetics at RCSI and associate director of FutureNeuro.

“[Our] research aims to change patient journeys, to result in faster, more precise diagnosis and fewer hospital and emergency department admissions.”

As Cavalleri explained, 30pc of those with an epilepsy diagnosis don’t respond to current treatment. The hope is that the scientists working at the centre can “drive the development of new therapies that work to restore normal brain function”.

FutureNeuro applies genomic sequencing to patients with epilepsy and related disorders, with the goal of identifying the exact genetic cause of an individual’s condition. When a particular mutation is identified, scientists can further examine a patient’s cells in a laboratory setting and gain startling insights.

‘The technology is quite remarkable. Scientists now have the ability to take a skin biopsy, grow those cells in the laboratory and then reprogram them to become various different cell types, including neurons’

“The technology is quite remarkable. Scientists now have the ability to take a skin biopsy, grow those cells in the laboratory and then reprogram them to become various different cell types, including neurons,” said Cavalleri.

“Once you have neurons containing the mutation of interest growing in the lab, the researchers can determine why the mutation might be causing disease, and perhaps what treatment might be appropriate to correct the problem.”

Translational projects

In addition to this research, FutureNeuro has undertaken collaborative projects with a number of different industry partners. It has partnered with UK medical firm Congenica (a spin-out from Wellcome Sanger Institute) to advance the company’s clinical genomics analysis software, Sapientia, to deliver faster and more accurate diagnoses in genetic epilepsy.

It has also joined forces with Irish biopharmaceutical SME GreenLight Medicines, which produces cannabis-based medicines, to focus on preclinical validation of the use of cannabinoids for childhood epilepsy, particularly exploring how cannabidiol (CBD) and other non-psychoactive molecules from the cannabis plant can reduce seizures.

Beyond the clinical

FutureNeuro’s work is massively enabled by advances in e-health, specifically the epilepsy electronic patient record (EPR), which was developed as a Lighthouse Project by the HSE and is currently spearheaded by Mary Fitzsimons. It contains detailed clinical information and patient-reported insights (seizure severity, meds compliance, quality of life etc) on 10,000 people with epilepsy in Ireland.

Fitzsimons is enthusiastic about the potential the programme has to improve clinical decision-making and support better research into the disorder when combined with genomic data. She hopes that the project can help “build a national understanding of the quality, safety and efficiency benefits of electronic health records”.

Fitzsimons is quick to add that the benefits of this project stem beyond the clinical – it also provides an economic opportunity for Ireland to become “a global leader in e-health technology development and use”.

As the research centre is in its nascent stages, operating within the hallowed halls of RCSI, it may be easy to allow such an organisation to fly under the radar of the general consciousness, just one of the many groups of scientists chipping away at the most challenging problems in health.

However, it is the clever leveraging of cutting-edge technologies that makes it clear FutureNeuro is something that should inspire deep excitement and anticipation over the amazing things that are likely to emerge.

Eva Short was a journalist at Silicon Republic