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Enlarged Prostate Drug May Have Potential for Motor Neuron Disease

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Motor neuron disease (MND) is a group of rare diseases that destroy nerve cells known as motor neurons, causing patients to slowly lose function of their muscles.


In studies using zebrafish, mice and stem cell models, experts have demonstrated that the drug terazosin protects against the death of motor neurons by increasing their energy production.


Researchers say the drug could help to slow the progression of a disease that affects around 5,000 adults in the UK. The average life expectancy is three years from the onset of symptoms.


The team are starting a feasibility study into the drug’s effect in MND patients. If this proves successful, they will look to launch a full clinical trial.

Energy production

It is still unclear why motor neurons die, but experts know that a decrease in their energy production takes place at an early stage of the disease.


Motor neurons need to produce energy to carry the brain’s instructions to the muscles. If there is not enough energy, the messages cannot be transferred effectively and movement is affected.


Researchers from the University of Edinburgh, working with partners at the University of Oxford, targeted the energy production of motor neurons as a potential therapeutic strategy for treating MND.


Using terazosin, which has previously been shown to be effective at increasing energy production in models of stroke and Parkinson’s disease, the team wanted to determine if this drug could also protect motor neurons from MND.

We are excited about the potential for terazosin to impact on the breakdown of motor neurons in MND. 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.

Professor Tom Gillingwater Professor of Anatomy at University of Edinburgh’s Euan MacDonald Centre for Motor Neuron Disease Research  and study co-lead

Enzyme target

They focused on an enzyme – an active molecule in the cells – involved in energy production called PGK1.


Zebrafish models of MND showed that either genetically increasing the amount of PGK1 in the zebrafish or treating them with terazosin to increase PGK1’s activity improved the growth of motor neurons.


Terazosin also protected motor neurons in a mouse model of MND, improving survival and delaying the progression of paralysis.


The team also grew motor neurons in a dish and demonstrated that terazosin protects these cells by increasing energy levels.

Our work shows that terazosin is protective of motor neuron cell death in multiple models of MND, making it an exciting new potential therapy. The benefit of working with terazosin is that it is already prescribed for a different health condition, so we know that it is safe for humans and could quickly move to the clinic.

Dr Helena Chaytow Senior postdoctoral researcher at University of Edinburgh’s Euan MacDonald Centre for Motor Neuron Disease Research and first author of the study

Feasibility study

To investigate this further the teams at the Universities of Edinburgh and Oxford are inviting 50 patients from the Oxford MND Care and Research Centre to participate in a feasibility study, which will examine the impact of terazosin on key indicators of disease progression.


The study is published in eBioMedicine. It was funded by MND Scotland and the My Name’5 Doddie Foundation.


Research at the University of Edinburgh was carried by a team at the Euan MacDonald Centre for Motor Neuron Disease Research, which was established by Euan MacDonald and his father Donald to improve the lives of people with MND.

 

As key funders of this research study, we are delighted to see a potential new therapy for MND on the horizon. After testing in a range of models, the results of this study show us that terazosin, a drug currently used to treat enlarged prostates and high blood pressure, may be able to protect motor neurons. We are delighted that, as a result, the drug will move to a feasibility study in Oxford, involving people living with MND. 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.
Dr Jane Haley MBE Director of Research for MND Scotland


The Foundation is encouraged that the collaborative nature of this work will aid translation from the lab to the clinic - it means that basic scientific research will be more meaningful in clinical practice. We are proud to have supported this collaboration and are continuing to support the first clinical trial of terazosin in people living with MND.
Jill Douglas CEO of My Name'5 Doddie Foundation

 

Reference: Chaytow H, Carroll E, Gordon D, et al. Targeting phosphoglycerate kinase 1 with terazosin improves motor neuron phenotypes in multiple models of amyotrophic lateral sclerosis. eBioMed. 2022. doi: 10.1016/j.ebiom.2022.104202

  

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