Edinburgh researchers show that medication previously approved and adopted for treating other conditions has potential as a “repurposed drug” therapy for Motor Neuron Disease (MND).

Research published today reveals that the drug – terazosin – is effective in zebrafish, mouse and stem cell studies for treating MND, following previous promising models for Parkinson’s Disease and strokes.

Terazosin – also known as Hytrin and Benph – is already used to treat high blood pressure and enlarged prostates, but research from the University of Edinburgh suggests the medication may also be effective as a new MND therapy.

Funded by MND Scotland and My Name'5 Doddie Foundation, the research team worked with a range of models to assess its potential use in MND and are now beginning studies in humans with collaborators in Oxford.

Describing a class of rare diseases that destroy nerve cells called ‘motor neurons’ used for communicating chemical signals from the brain or spinal cord to muscles and glands, MND incidence in Scotland has increased over the past 20 years.

Zebrafish and mouse models

Dr Helena Chaytow, a postdoctoral researcher from the University of Edinburgh and lead author of a paper outlining this work, explained that early success of the high blood pressure drug was confirmed in zebrafish MND models.

She said they initially found it had a protective impact on the health of motor neurons and even the motor behaviour of zebrafish in all the models they tested.

The team validated their work in mouse models and confirmed in stem cell derived motor neurons that terazosin can increase energy production to protect against cell death. Dr Chaytow added:

“Suddenly we realised we had this complete story with so much evidence of traces and being protective that we could move it forward into the clinic.”

MND affects around 400 people in Scotland and 5,000 people across the UK and average life expectancy following diagnosis is just 18 months. Now, Dr Chaytow says that terazosin presents “an exciting new potential therapy” that could help slow the progression of the disease.

Understanding MND

She explained the drug can increase energy production in motor neurons, which is key to their therapeutic strategy as, while the mechanism of MND is currently unknown, it is understood to be strongly related with a decline in energy.

Without consistent energy production in motor neurons, they can no longer provide the communication pathways essential for speech, breathing, or movement as people progressively lose muscle function.

Dr Chaytow also highlighted the benefit of working with terazosin is that it has surpassed a previous challenge by already being approved for other conditions, allowing it expedite the clinical testing stages.

Dr Jane Haley MBE, Director of Research for MND Scotland, said: “As key funders of this research study, we are delighted to see a potential new therapy for MND on the horizon.”

Collaborating across Edinburgh and Oxford, the team focused on a particularly active enzyme in the energy production pathway for motor neurons. Dr Chaytow explained that by targeting this PGK1 enzyme and increasing its activity, the energy available to motor neurons is increased:

“By increasing the amount of energy available for the cell, we hope that the motor neurons will be able to overcome the disease pathways so that it prolongs the life of the motor neurons, extending the disease course.”

Perotective potential

Moving to mouse and stem cell models of MND, terazosin was also found to be protective of motor neurons, slowing the progression of paralysis and improving survival of cells by increasing the available energy.

Professor Tom Gillingwater, Professor of Anatomy at the Euan MacDonald Centre at the University of Edinburgh, and study co-lead, said:

“The current work illustrates the importance of bringing together scientists and clinicians in order to identify new targets for therapy suitable for taking forward into studies in human MND patients.”

A total of 50 patients have now been invited to participate in feasibility studies in Oxford so  researchers can monitor the impact of the drug on disease progression.

Dr Haley said that MND Scotland are delighted that the protective results for motor neurons are promising. She added:

“This is a wonderful example of researchers, clinicians and MND charities working together to try and speed up the search for new treatments for MND – because it’s about time we found a cure.”

One challenge facing the future of MND research and the team’s feasibility studies, according to Dr Chaytow, is the variability of disease pathways in patients with MND. Researchers aim to control for this by using a similar group of patients, but individual differences between them may obscure the true effectiveness of treatment.

The Scottish government’s Neurological Care and Support Framework included future workforce expansion and treatment research on MND in Scotland as part of its focus for 2020-2025.

Read more: Treatment delays for neurological conditions; Young people help write epilepsy guidance; MND research receives £45,000 charity funding

Sign up to our bulletin for key health & social care updates straight to your inbox and you can follow healthandcare.scot on Google News.