Compelling research, led by a team from the University of California, Santa Barbara, has discovered a drug originally developed as a cancer treatment may be repurposed to target a variety of neurodegenerative diseases including Alzheimer's. Despite proving to be ineffective in treating cancer, the new drug has been shown to be safe for humans and early mouse studies suggest it could have potential as a new dementia treatment.

Alzheimer's research has undeniably been in a major state of flux over the past few years. Just last week yet another major drug failed in late stage human trials after years of work and millions of dollars of funding. Almost every major Alzheimer's drug failure over the years has targeted the accumulation of a protein in the brain called beta-amyloid.

The amyloid hypothesis has dominated Alzheimer's research for a couple of decades now, however, every drug designed to target the accumulation of these toxic proteins has failed at some stage in human testing. Researchers have also studied another protein called tau thathas been found to accumulate in the brains of Alzheimer's sufferers.

Misfolded tau proteins, called neurofibrillary tangles, tend to appear in the brains of people with Alzheimer's much later than amyloid plaques, although there are other neurodegenerative diseases known to be entirely driven by the accumulation of these tau tangles.

Kenneth Kosik, co-director of the Neuroscience Research Unit at UC Santa Barbara, has been investigating the associations between tau and neurodegenerative diseases for several decades. The latest study published by Kosik and his collaborators is the culmination of years of work leading to an understanding of what specific genes and proteins guide the formation of abnormal tau tangles in the brain.

Prior research had revealed that a specific protein called Rhes was abnormally activated in patients suffering from genetic mutations that result in tau-related neurodegenerative disease. This led the researchers to look at a drug that had already been developed to inhibit the activity of that specific protein.

"It turns out the drugs in this category, called farnesyltransferase inhibitors, have been tested in humans," says Kosik. "They're safe. But, they did not work in cancer."

Called lonafarnib, the drug was originally designed to interrupt tumor growth in a variety of cancers but human trials found it to be relatively ineffective for that purpose. Hypothesizing the drug to potentially be effective in disrupting the process that causes tau tangles, the researchers embarked upon a series of mouse experiments that provided dramatically positive results.

"To test this drug we used genetically engineered mice that develop human tau tangles and then dementia," Kosik explains in commentary penned for The Conversation. "Such animals often run in circles. But when we fed these animals lonafarnib, the drug blocked the formation of the tau tangles in the brain and the abnormal behavior. When tau tangles disrupt the normal brain activity, the mice are unable to build nests. But the mice receiving the drug proceeded with nest-building and other normal behaviors. Mice that were untreated all developed dementia."

Of course, the story of Alzheimer's research is littered with a near-constant parade of promising animal studies that simply haven't be replicated in human trials. So while this is an exciting piece of research, Kosik and his team are well aware of the challenges ahead.

Perhaps the biggest hurdle the researchers currently face is obtaining more lonafarnib so human trials can commence. Eiger BioPharmaceuticals, the company behind the drug, are reportedly reticent to make the drug available for Kosik's research. The company is primarily working through trials using the drug to treat progeria, a rare genetic condition that causes children to rapidly age.

Kosik and his team are currently trying to access more lonafarnib to continue their research.

The new research was published in the journal Science Translational Medicine.