Reversing dementia in mice
Paige Cramer is a newly minted Ph.D working in Gary Landreth’s Alzeimer’s lab at Case.  She’s talking about mice that are bred to develop the disease.  These mice, as they age, forget familiar smells, lose their natural fear and stop doing what mice love best -- shredding paper.  

“They don’t make a nest. In fact, they don’t know what to do with the pieces of pressed paper.”

But when Cramer gave these Alzheimer’s mice a dose of the drug bexarotene:

“They actually began to return this affiliative behavior of making nests.”

A new use for bexarotene
Bexarotene is not a new drug. It’s been used for more than a decade to treat a form of skin cancer. But Landreth and his team have uncovered its potential for treating Alzheimer’s.

“If humans are like mice, or vice versa, we may have a drug which appears might be effective in the earliest stages of Alzheimer’s disease.”

Their breakthrough didn’t come easy. First of all no one knows exactly what causes Alzheimer’s disease.  Doctor Alois Alzheimer first described the disease in 1906, and he was the first to implicate the build-up of a protein fragment called beta-amyloid as causing the fatal decline he saw in his patient.

Gary Landreth agrees, even though he says amyloid is a normal part of brain function.

“As you’re talking to me, we are producing amyloid --  these small sticky peptides -- as a normal consequence of electrical behavior in the brain.”

Landreth says the problem is that as we get older our brains become less efficient at clearing away the amyloid gunk.

“Just like everything else in aging, some of us will perform this function less efficiently.  Amyloid accumulates in the brain, it poisons the communication systems between neurons, and this underlies the cognitive deficits.”

The breakthrough 
Landreth’s breakthrough in developing a new treatment for Alzheimer’s came after a decade of work unlocking the genetic causes of the disease. 

He targeted a variant of the gene called ApoE that occurs in 80 percent of people with Alzheimer’s.  

“We recognized that ApoE was part of a garbage-disposal mechanism, whereby amyloid could be eliminated from the brain. That was the breakthrough.”

Landreth reasoned that a drug that stimulated that gene would aid the removal of amyloid from the brain and reduce the symptoms of Alzheimer’s. That’s what he and his team saw with bexarotene.

But lead researcher Paige Cramer cautions that curing mice is not the same as curing people.

“I would hold off on saying it’s the next treatment for Alzheimer’s disease until we get some data in humans.”

Uncharted territory
Proven or not, in the weeks since their findings were published, Landreth and Cramer have received thousands of calls from people seeking  treatment for loved ones with Alzheimer’s.

Over the years hundreds of drugs have been tested and none have reversed the effects of Alzheimer’s.

Still Landreth and Cramer feel optimistic enough to form a company, RexCeptor, to run the clinical trials for their Alzheimer’s drug. 

“This is new territory, it’s uncharted, uncharted waters. And it’s not clear exactly how this is going to proceed.”

The team estimates another year of testing the treatment in mice, then several years of trials in humans before the drug, if it works, will be available for Alzheimer’s patients.

For now they refer all inquiries to the Alzheimer's Association at alz.org.