Trinity College researchers to participate in gene-based clinical trial for motor neuron disease

Reviewed by Emily Henderson, B.Sc.Sep 2 2020

Researchers at Trinity College Dublin are to participate in an early phase gene-based clinical trial for motor neuron disease (MND). The research team represents one of only four centres in Europe to take part in such an exciting clinical trial for this devastating disease. The first Irish patient will enter the study today, (Tuesday, 1st September, 2020) at the Clinical Research Facility at St James's Hospital Dublin.

MND is a devastating condition which causes progressive paralysis, increasing physical disability and ultimately death within an average of two to three years. There are over 350 people in Ireland with MND, and one person is diagnosed every 3 days with the condition. There is currently no effective treatment.

The clinical trial, sponsored by the US Pharmaceutical Company Biogen, targets an abnormal expansion of the MND-associated gene C90rf72 using a novel gene therapy that is designed to switch off the abnormal part of the gene. Up to 10% of all people diagnosed in Ireland with MND carry the abnormal C9orf72 gene, which can cause both MND and dementia.

The Phase 1 trial which has been divided into 5 sections involving 75 patients worldwide, was recently approved by the HPRA (Health Products Regulatory Authority).. Only 24 patients in the world will be enrolled in the fifth section , including the first Irish patient to enter the study.

Professor Orla Hardiman, Principal Investigator in the Irish part of the study and a leading world authority on MND said:

"Up to 10% of people in Ireland with MND carry an abnormal expansion of the C9orf72 gene. Gene therapy is an exciting new approach and considerable progress has already been made in turning off another MND associated gene ( SOD1), as the results of early clinical trials have shown. We are very hopeful that the same approach will work for those with the C9orf72 gene. "

Earlier this summer, Professor Hardiman provided an invited editorial for the New England Journal of Medicine commenting on these early trials using gene therapy for SOD1. "While we do not have any patients with SOD1 mutations in Ireland, we have many people carrying the abnormal C9orf72 gene, and for these people, the current trial could be a true gamechanger," she said. "And the pharmaceutical industry is also looking at other modifier genes that we could target, which could help many other people with MND who do not carry the C9orf72 mutation. While these are early days, there is now genuine hope that MND will become a treatable disease in the near future," she said.

The trial is currently being conducted at the Trinity College/St. James's Hospital Clinical Research Facility CRF), which has been fully equipped for these precision medicine-based gene therapy trials. Our aim is to be the leading centre in the country for these types of early phase studies and we are delighted that the HPRA has pre-inspected and approved us. Ireland has traditionally not been able to compete on the world stage for these types of very early clinical trials, and it is a testimony to our staff, and to the international reputation of the Irish MND Research Group that we have been selected and approved to enrol an Irish patient into this study."

Professor Martina Hennessy, Director of the St. James's Clinical Research Facility