In studies using zebrafish, mice, and stem cell models, researchers from the University of Edinburgh (working with collaborators at the University of Oxford) demonstrated that the drug terazosin protects against the death of motor neurons by increasing their energy production.

Their study, published August 10 in the journal eBioMedicine, reported that zebrafish models of MND showed that either genetically increasing the amount of the enzyme phosphoglycerate kinase 1 (PGK1) in the zebrafish or treating them with terazosin to increase PGK1's activity improved the growth of motor neurons.

The researchers also found that terazosin protected motor neurons in a mouse model of MND, improving survival and delaying the progression of paralysis, while growing motor neurons in a dish 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," Helena Chaytow, PhD, the study's first author and senior postdoctoral researcher at University of Edinburgh's Euan MacDonald Centre, said in a statement.

Next, as part of a feasibility study, the researchers are planning to invite 50 patients from the Oxford MND Care and Research Centre to examine the impact of terazosin on key indicators of disease progression.

"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," said study co-lead Dr. Kevin Talbot, a neurologist and professor of motor neuron biology at the University of Oxford.

In 2019, researchers from China, Spain, and the University of Iowa showed evidence that terazosin may improve Parkinson's disease (PD) symptoms. The results from experimental models and clinical database analysis, published in the Journal of Clinical Investigation, suggested that enhancing PGK1 activity and increasing glycolysis may slow neurodegeneration in PD.

Gene therapy shows promise in treating ALS in rodent models
A gene therapy, patented through the University of California, San Diego and the Department of Veterans Affairs measurably delayed disease onset in humanized...

Insilico Med, 4B Tech partner on neurodegenerative drug discovery
Insilico Medicine is collaborating with 4B Technologies to develop small-molecule therapies for amyotrophic lateral sclerosis and other major neurological...

Ionis doses ALS patients with antisense medicine in clinical trial
Ionis Pharmaceuticals has dosed the first patients with ION541, an investigational antisense medicine developed to treat most forms of amyotrophic lateral...