Scientists find drug used to treat glaucoma could help in fight against dementia

A drug commonly used to treat glaucoma has been shown to protect against the build-up of a protein that causes various forms of dementia in animal trials.

Researchers in the UK Dementia Research Institute at the University of Cambridge screened more than 1,400 clinically-approved drug compounds using zebrafish and found carbonic anhydrase inhibitors – such as the glaucoma drug methazolamide – clear build-up of the tau protein and reduce signs of the disease in zebrafish and mice.

The zebrafish are genetically engineered to make them mimic so-called tauopathies, which are neurodegenerative diseases characterised by the build-up in the brain of tau protein and include forms of dementia, Pick's disease and progressive supranuclear palsy, Alzheimer’s disease and neurodegeneration caused by repeated head trauma, as has been reported in football and rugby players.

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There has been little progress in finding effective drugs to treat these conditions. One option is to repurpose existing drugs. However, drug screening – where compounds are tested against disease models – usually takes place in cell cultures, but these do not capture many of the characteristics of tau build-up in a living organism.

To work around this, the Cambridge team turned to zebrafish models they had previously developed. Zebrafish grow to maturity and are able to breed within two to three months and produce large numbers of offspring. Using genetic manipulation, it is possible to mimic human diseases as many genes responsible for human diseases often have equivalents in the zebrafish.

Dr Ana Lopez Ramirez from the Cambridge Institute for Medical Research, Department of Physiology, Development and Neuroscience and the UK Dementia Research Institute at the University of Cambridge, said: “Zebrafish provide a much more effective and realistic way of screening drug compounds than using cell cultures, which function quite differently to living organisms. They also enable us to do so at scale, something that it not feasible or ethical in larger animals such as mice.”

Professor Rubinsztein from the UK Dementia Research Institute and Cambridge Institute for Medical Research at the University of Cambridge, adds: “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. This will enable us to move to clinical trials much faster than we might normally expect if we were starting from scratch with an unknown drug compound.

“This shows how we can use zebrafish to test whether existing drugs might be repurposed to tackle different diseases, potentially speeding up significantly the drug discovery process.”