Summary: Researchers at the University of Cambridge have discovered that methazolamide, a drug commonly used to treat glaucoma, may help prevent the build-up of tau protein in the brain – a key factor in various forms of dementia including Alzheimer’s disease. The breakthrough study, which screened over 1,400 existing drugs using zebrafish and mice models, offers hope for repurposing an already approved medication to combat neurodegenerative diseases.
Journal: Nature Chemical Biology, October 31, 2024, DOI: 10.1038/s41589-024-01762-7
Reading time: 4 minutes
A Novel Approach to Drug Discovery
In a groundbreaking study, UK researchers have identified an unexpected ally in the fight against dementia: a common glaucoma medication. The discovery came through an innovative screening process that tested over 1,400 approved drugs using zebrafish, chosen for their unique advantages in medical research.
“Zebrafish provide a much more effective and realistic way of screening drug compounds than using cell cultures, which function quite differently to living organisms,” explains Dr. Ana Lopez Ramirez, joint first author of the study. “They also enable us to do so at scale, something that it not feasible or ethical in larger animals such as mice.”
How the Drug Works
The research team found that methazolamide works by inhibiting an enzyme called carbonic anhydrase, which helps regulate cell acidity. This inhibition triggers an unexpected response: it causes the cell’s waste disposal units (lysosomes) to move to the cell surface and expel harmful tau protein accumulations.
In mouse studies, animals treated with methazolamide showed improved memory and cognitive performance compared to untreated mice. Their brains also contained fewer tau aggregates and showed better preservation of brain cells.
Fast Track to Clinical Trials
Professor Rubinsztein from the UK Dementia Research Institute notes the significant advantage of discovering new uses for existing drugs: “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.”
Glossary
- Tauopathies: Neurodegenerative diseases characterized by the build-up of tau protein in the brain
- Carbonic anhydrase: An enzyme that helps regulate acidity levels in cells
- Lysosomes: Cell structures that break down and dispose of cellular waste
- Methazolamide: A carbonic anhydrase inhibitor commonly used to treat glaucoma
Reader Quiz
- Q: How many drug compounds were screened in this study?
A: Over 1,400 clinically-approved compounds - Q: Why were zebrafish chosen for initial drug screening?
A: They provide a more realistic model than cell cultures and enable large-scale testing - Q: What is the mechanism by which the drug helps clear tau protein?
A: It causes lysosomes to move to the cell surface and expel tau proteins - Q: What advantage does using an existing drug provide?
A: Its safety profile is already known, enabling faster progression to clinical trials
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