Scientists failed to replicate the tantalizing evidence of efficacy from a study of the cancer drug bexarotene in mouse models of Alzheimer's disease, throwing cold water on efforts to advance the approved anti-tumor therapy for patients with the memory-stealing illness. And the latest findings add to a long list of setbacks in the Alzheimer's field, which has failed to produce a single drug to reverse the disorder, despite billions of dollars in research spending over many years.
Today the journal Science published a series of articles based on a recent round of independent studies that poke gaping holes in the findings published in the journal in early 2012, when neuroscientist Gary Landreth from Case Western Reserve University School of Medicine and his collaborators reported that bexarotene wiped out half of the beta amyloid plaques associated with Alzheimer's in a few days and improved cognitive functions in mice. The study sparked a frenzy of interest from Alzheimer's victims in the cancer drug, which Eisai markets for skin cancer.
Landreth has even formed a biotech startup, ReXceptor, and has raised more than a $1 million to fund research of bexarotene for Alzheimer's disease. The upstart has launched a Phase I study in healthy volunteers, and Landreth told Reuters that he expects data before Christmas. The Case Western neuroscientist has pointed out that independent research confirmed that the drug could reduce free-floating amyloid proteins, which have been linked with toxicity in patients and contributing to the formation of plaques.
A lab from the University of Pittsburgh, which was one of several labs to test Landreth's approach, also found that the cancer drug reduced cognitive impairment. However, other researchers failed to observe that mental benefit, and one lab from the University of Florida College of Medicine reported an inability to find that bexarotene could eliminate the plaques or the free-floating proteins. This left plenty of questions for Landreth and his colleagues to answer.
"It was our expectation other people would be able to repeat this," Landreth said, as quoted by Nature. "Turns out that wasn't the case, and we fundamentally don't understand that."
Experts had already advised doctors to resist pleas for prescriptions of the cancer drug for the unproven use in Alzheimer's disease. The latest mouse studies bolster arguments against off-label use of the drug for Alzheimer's, not to mention that anti-amyloid drugs from Eli Lilly ($LLY), Pfizer ($PFE) and others have crashed and burned in Phase III studies over the past year. The jury is still out on the amyloid theory for combating the disease, which affects 5.4 million Americans and growing.