Terazosin, a drug currently approved to treat high blood pressure and enlarged prostate, may also be able to treat ALS. The corresponding study was published in eBioMedicine.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with a complex genetic background. The mean survival rate for those with the condition is two to five years. However, some can live for ten years or longer. Common symptoms include progressive muscle weakness and paralysis. There is currently no cure for the condition.
Previous studies have reported that terazosin can increase energy production in neurons in models of stroke and Parkinson’s disease. In the current study, researchers sought to see if the drug may similarly benefit motor neuron conditions such as ALS.
Through a variety of experiments, researchers found that terazosin protects against the death of motor neurons by increasing their energy production. Motor neurons need to produce energy to transmit signals from the brain to the body’s muscles. If they have insufficient energy, signals cannot be carried, ultimately disrupting movement of the body.
In particular, the researchers focused their attention on how terazosin affects the enzyme PGK1, which is involved in energy production. In zebrafish models of motor neuron disease, they found that both genetically increasing PGK1 levels and treatment via terazosin independently increased PGK1 activity and improved the growth of motor neurons.
The researchers also found that terazosin protected motor neurons in a mouse model of motor neuron disease, improved survival, and delayed progression into paralysis.
The team now wishes to investigate the ability of terazosin to treat motor neuron diseases in human patients. To this end, they are currently inviting 50 patients with the condition to participate in a feasibility study to examine the drug's impact on key indicators of disease progression.
Professor Kevin Talbot, Professor of Motor Neuron Biology at the University of Oxford and study co-lead, said: “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.”
Dr. Helena Chaytow, a senior postdoctoral researcher at the University of Edinburgh’s Euan MacDonald Centre and first author of the study, said: “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.”