Animal studies have shown the potential of a drug commonly used to treat glaucoma — a chronic eye disease — in fighting against dementia.
Researchers in the UK Dementia Research Institute at the University of Cambridge in the UK focused on a class of drugs known as carbonic anhydrase inhibitors — of which the glaucoma drug methazolamide is a part. They found it can prevent the build-up of the protein tau — linked to various forms of dementia in the brain.
Using genetically engineered zebrafish that could mimic so-called tauopathies, the team screened more than 1,400 clinically-approved drug compounds. Tauopathies are neurodegenerative diseases characterised by the build-up in the brain of tau protein ‘aggregates’ within nerve cells.
The researchers found that the drugs can help clear tau build-up and reduce signs of the disease in zebrafish. The tau build up was also cleared in mice with the P301S human disease-causing mutation, which can lead to Alzheimer’s, Pick’s disease and progressive supranuclear palsy, they noted in the paper published in the journal Nature Chemical Biology. To understand the untreatable conditions, the team modelled tauopathy in zebrafish and screened 1,437 drug compounds.
In the genetically engineered mice, a treatment with methazolamide helped them perform better at memory tasks and also led to improved cognitive performance compared with untreated mice. Analysis of the mouse brains showed that they indeed had fewer tau aggregates, and consequently a lesser reduction in brain cells, compared with the untreated mice.
“Methazolamide shows promise as a much-needed drug to help prevent the build-up of dangerous tau proteins in the brain. Although we’ve only looked at its effects in zebrafish and mice, so it is still early days, we at least know about this drug’s safety profile in patients,” said Professor Rubinsztein from the UK Dementia Research Institute at the University of Cambridge.
