Alzheimer's drugs better in combination, study says

Alzheimer's disease may be better treated with a mix of drug therapies that limit production of plaque that impairs the brain rather than with one treatment alone, a study in mice suggests.

The combination approach preserved memory with few side effects, something individual treatment methods haven't been able to do as well, researchers at Johns Hopkins University School of Medicine said in a report published yesterday in the journal Science Translational Medicine.

There's no cure yet for Alzheimer's, a disease that attacks the brain and causes memory loss that can devolve into severe cognitive decline. It affects an estimated 30 million people worldwide and was the sixth-leading cause of death in the United States in 2007, according to the Centers for Disease Control and Prevention in Atlanta.

Scientists suspect Alzheimer's may be caused by a protein called amyloid beta, generated by two enzymes that drugmakers have been targeting individually with experimental treatments.

"The idea is if you can identify compounds or drugs that inhibit these enzymes, you'll be able to slow down the progression of the disease," said Philip Wong, a professor in the pathology and neuroscience departments at Johns Hopkins who was a senior author of the study. "One of the major issues is side effects."

Two enzymes known to spur formation of amyloid beta that afflicts brain function are beta-secretase and gamma-secretase, both targets in Wong's study of mice.

Drugmakers are working on treatments that aim to inhibit either enzyme, Wong said. Lilly's semagacestat, a gamma-secretase inhibitor, is in the final stage of human trials generally required for U.S. approval, the company said in December.

The idea of targeting both enzymes simultaneously is "completely novel," Wong said.

Drugs will have to be approved for use individually before they would be able to be combined, making the prospect of human testing with a potential cocktail years away, he said.

Completely blocking either enzyme can cause side effects such as skin cancer, schizophrenia-like symptoms and shortened lifespan, Wong said. Partly inhibiting them cut the side effects and still helped reduce plaque production, Wong said.