Does a disease modifying drug for motor neuron disease already exist?
A recent study has highlighted the potential for a drug, previously used to treat high blood pressure, to be repurposed to help treat motor neuron disease.
Motor neuron disease (MND), also known as amyotrophic lateral sclerosis (ALS), encompasses a collection of rare conditions affecting the brain and nerves. A reduction in energy production within the motor neurons takes place in the early stages of the disease, with subsequent neuronal damage causing individuals to lose their muscular ability. It remains unknown as to why the motor neurons cease to function, highlighting the need for further research in this area in order to progress towards a cure. In light of this, a recent study from the University of Edinburgh (UK), working alongside the University of Oxford (UK), has identified a potential drug repurposing opportunity for the treatment of MND.
Previously used to treat high blood pressure and enlarged prostates, the role of the drug terazosin in preventing neuronal cell death is also well established. In vivo and in vitro models have highlighted its ability to promote motor neuron energy production in the context of both Parkinson’s disease and stroke. This recent study aimed to evaluate whether terazosin was able to slow the progression of MND, and if it would therefore be an effective therapeutic avenue.
The research team took two initial approaches: genetically engineering zebrafish models to overexpress PGK1, an enzyme involved in energy production, or treating the models with terazosin. Both approaches were found to increase the overall activity of PGK1, and subsequent growth of motor neurons. Building upon this, the team provided further in vivo evidence, as terazosin was found to prevent progression of paralysis and improve survival in MND mouse models.
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Helena Chaytow (University of Edinburgh) commented: “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.”
Teams from both collaborating universities are continuing this line of research by inviting 50 patients from the Oxford MND Care and Research Centre (UK) to take part in a study evaluating the effect of terazosin on factors known to promote MND disease progression.
Kevin Talbot (University of Oxford) stated: “We urgently need to accelerate the way drugs are developed from laboratory models into trials in patients. Our work uses a combination of approaches to increase the confidence that drugs will actually work in people with MND and significantly slow disease progression. It represents an important new step in the search for therapies.”