The Problem of Replication

Massachusetts General
  • Linda Keslar

In 2012, when the journal Science published a study by a group of Cleveland researchers touting a cancer drug’s success against Alzheimer’s disease in mice, it looked like a potential breakthrough in a field long marked by setbacks and failures. As many as 5.4 million Americans have Alzheimer’s, and by one estimate, there’s a new case diagnosed every 69 seconds. While existing treatments can alleviate symptoms, there’s nothing to stop the progression of the ultimately fatal disease.

But in this study, researchers from Case Western Reserve University School of Medicine described how a drug called bexarotene appeared to clear the buildup of amyloid-beta plaques—protein deposits in the brain that are hallmarks of Alzheimer’s—in mice genetically engineered to have a condition similar to the human disease. The drug also seemed to improve the mice’s memory, cognitive abilities and social behavior. “The plaque reduction was an astounding finding,” says Sangram Sisodia, director of the Center for Molecular Neurobiology at the University of Chicago.

No other drug had attacked the plaques so rapidly. Bexarotene, marketed under the brand name Targretin, belongs to the retinoid class of drugs, related to vitamin A, that had been approved by the Food and Drug Administration in 1999 to treat a type of skin cancer called cutaneous T-cell lymphoma. According to the study in Science, bexarotene activated a gene that boosts production of apolipoprotein E, or ApoE, which can help break down amyloid-beta. Alzheimer’s patients can’t produce enough ApoE to prevent the protein from creating deposits. The drug also seemed to rouse a cellular mechanism that consumes the plaques.

Sisodia was one of many scientists who rushed to replicate the original study. “I think we all went back to our labs and tried to confirm these promising findings by repeating the initial experiments,” he says. Rudolph Tanzi, director of the genetics and aging research unit at Massachusetts General Hospital, also sought to repeat the research, spurred in part by physicians whose patients had heard about the apparent breakthrough and wanted to start taking bexarotene immediately. That was such a common response that in August 2012, The New England Journal of Medicine published an article warning physicians to wait for evidence from human clinical trials. “The results in mice certainly didn’t guarantee the drug would work in people,” says Tanzi. “And although it’s safe for cancer treatment, it can have severe side effects.”

(continued)

More From Massachusetts General >>
Read Next Article >>
Got grapes? UCLA researchers have demonstrated how resveratrol, an antioxidant derived from grapes...
UCLA has been tapped by the Defense Advanced Research Projects Agency to spearhead an innovative...
Harry Campbell
Neurologist Bruce Miller calls tau—a floppy, free-form protein—“the holy grail of dementia.” That...
Physicians have long assumed that ovarian cancer—one of the deadliest cancers among women—...
Wrong-level spine surgeries—when a surgeon accidentally operates on the wrong vertebra—occur with...
Photo by Sam Kaplan; Copyright Sam Kaplan
In 2012, when the journal Science published a study by a group of Cleveland researchers touting a...
Photo by Movus; http://www.gettyimages.com
Patients who come to Johns Hopkins for epilepsy surgery sometimes require a prequel to their...
Copyright Getty Images
In the late 1990s, the process of isolating genes from the chromosomes in which they reside was...
Photo by Sergey Anatolievich Pristyazhnyuk; copyright Getty Images
The human body has many natural barriers intended to prevent microorganisms, diseases, and toxins...
Illustration by Brian Stauffer
 When Fred Lesikar arrived at the hospital in October 2009 suffering sharp pain in his upper back,...