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A Long-Standing Antibiotic Offers A New Path Against Alzheimer's


Stephen Luntz

Stephen has a science degree with a major in physics, an arts degree with majors in English Literature and History and Philosophy of Science and a Graduate Diploma in Science Communication.

Freelance Writer

hippo mouse

These amalyoid beta plaques in a mouse hippocampus are indicative of Alzheimer's disease, but a molecule derived from an antibiotic prevents their formation. Yale University

In the tradition of scientific breakthroughs often coming from very unexpected places, an antibiotic in use since 1989 has shown potential for breaking the cycle that leads to Alzheimer's disease. Given the failure rate of initially promising drugs against Alzheimer's, there is a long way to go on this one. Nevertheless, the fact the drug in question involves a fundamentally different approach to stopping the neurological disease than most of those tried so far could mean it's just what we need.

The symptoms of Alzheimer’s are hard to tell apart from less common forms of dementia. Its distinguishing feature is the presence of amyloid beta plaques on the brain that spread as the disease progresses. Most experimental drugs break up the plaques. However, there has always been a minority of neuroscientists who see the plaques as a symptom, not the fundamental cause of Alzheimer's. The failure of plaque-dispersing drugs has given strength to their calls for alternative approaches, usually in trying to disrupt the chain of events that triggers the plaque build up.


Professor Stephen Strittmatter of Yale University is pursuing one alternative by looking at the signaling mechanism that triggers plaque formation. He hopes disrupting the interaction between the protein PrPC and amyloid beta would prevent the onset of Alzheimer's.

Strittmatter and his colleagues tested 2,560 existing drugs and 10,000 other molecules for their potential, and the clear stand-out was cefixime, which is an antibiotic still used for gonorrhea and pneumonia (despite sounding like a character from the Asterix cartoons).

Further testing indicated cefixime itself does not function as necessary. However, over several days at room temperature cefixime degrades into a polymer that does indeed disrupt amyloid beta/PrPC interactions.

The Yale team created more effective versions of the polymer, particularly with the capacity to cross the blood-brain barrier. They announced in Cell Reports these not only prevent mice from developing dementia, but actually give them space to repair their brains so their ability to navigate through a maze by memory improves.


PrPC is a prion, the bizarre category of proteins that cause Creutzfeldt-Jakob and Mad Cow Disease, so Strittmatter tested his polymer in cells infected with Creutzfeldt-Jakob prions. It appeared similarly effective, although the ultimate success rate of drugs tested only in cell cultures is much lower than for those that have also worked on animals.

It is always a long, slow process for drugs to make their way from animal testing to clinical use, and as the history of Alzheimer's therapies shows, one often littered with failures. However, the process is considerably shorter where drugs have already been put to other purposes and shown to be safe. Unlike cefixime, Strittmatter's optimized polymer hasn't had this testing, but the established record of several closely related drugs raises hopes it will prove safe.


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