Cancer drug shows promise in mouse Alzheimer’s study

Friday, 10 February 2012

Mice in the early stage of Alzheimer’s disease had some of their brain abnormalities reversed and their declining mental function restored when they were given low doses of a rarely used cancer drug.

The drug, bexarotene, stimulated removal of beta-amyloid, a substance whose accumulation in the brain appears to be the main cause of Alzheimer’s dementia. After treatment, the animals fared better in tests of memory and social behavior, according to a study published online Thursday by the journal Science.

The findings were dramatic but their relevance to people with Alzheimer’s disease is unknown. But because the drug is already approved for human use, finding out may be easier than if the drug were an entirely new chemical compound.

“It has to work in humans like it works in mice or we can pick up and go home,” said Gary E. Landreth, a neuroscientist at Case Western Reserve University School of Medicine who headed up the experiment.

A study of bexarotene’s effects in normal brains will start in a few months. Clinical trials in people with early Alzheimer’s — or at high risk for the disease for genetic reasons — will take years, if they occur at all. Nevertheless, the researchers think speed is important, as they fear people might start using the drug before it’s fully evaluated.

“We’ve got to work fast and we have got to be right. We can’t screw this up,” Landreth said.

Bexarotene is a member of the retinoid family of compounds, which are all chemically related to vitamin A. Retinoids have effects on cell division and growth, immunity and other essential biological functions.

Sold under the trade name Targretin, bexarotene is approved by the Food and Drug Administration as a treatment for cutaneous T-cell lymphoma, a disease diagnosed in about 3,000 Americans a year. It is an “orphan drug,” a designation that gives drug companies an incentive to develop medicines for rare diseases. Orphan drugs stay under patent protection longer than regular drugs. It has been tried against other forms of cancer, without impressive results.

Numerous “candidate” Alzheimer’s drugs, promising in lab studies, have washed out in recent years.

In 2011, Pfizer and a small partner announced they were abandoning a drug called Dimebon after numerous failures to show benefit in people. In 2010, Lilly halted development of a different compound, semagacestat. At the Alzheimer’s Association, an advocacy organization, the new study’s results were greeted with that history in mind.

“This is an early study and it was in mice,” said Maria C. Carrillo, the organization’s director of scientific relations. “We need to be cautiously optimistic and pursue this lead as we would any other.” She added that what makes “this an exciting study is that it involves a repurposed drug.”

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