HEALTH - Alzheimer's Gene?

"In Preventing Alzheimer’s, Mutation May Aid Drug Quest" by GINA KOLATA, New York Times 7/11/2012

Excerpt

A study of a rare gene mutation that protects people against Alzheimer’s disease provides the strongest evidence yet that excessive levels of a normal brain substance, beta amyloid, are a driving force in the disease — bolstering hopes that anti-amyloid drugs already under development might alter the disease’s course or even prevent it.

So far, the drugs have not succeeded. But scientists not connected with the new study said it suggested that the drug companies’ big bets on anti-amyloid treatments could yet pay off.

The implication for drug development “is hugely important,” said Dr. David Altshuler, a genomics expert at Harvard Medical School and the Broad Institute of Harvard and M.I.T.

And Dr. Samuel Gandy, an Alzheimer’s researcher who directs the Mount Sinai Center for Cognitive Health, called the finding the most significant in the field in two decades, since researchers first reported a mutation that leads to the disease.

The protective mutation, whose discovery was reported online Wednesday in the journal Nature, is highly uncommon — it is not the reason most people do not develop Alzheimer’s. But what intrigues researchers is how it protects the brain.

Mutations that cause Alzheimer’s lead to excessive amounts of beta amyloid in the brain; by contrast, the protective mutation slows beta amyloid production, so people make much less.

“This paper provides strong evidence that it would work in the general population if you did it right,” Dr. Altshuler said.

Scientists at the drug companies agreed. “We are thrilled,” said Ryan Watts, one of the authors of the new paper and head of the neurodegeneration labs at Genentech, which is developing two drugs to reduce brain amyloid levels.

Dr. Richard Mohs, leader of neuroscience early clinical development at Eli Lilly, said the company was “very encouraged by these study results.” They show, he said, that despite an initial failure, the strategy of focusing on drugs to reduce beta amyloid levels is “a logical path for the development of effective therapies that may slow disease progression.”

Many questions remain, of course. Most people do not have the protective gene mutation, but as common as Alzheimer’s is, most people do not get it. It is not clear why. And most who develop Alzheimer’s do not have one of the rare gene mutations that cause it. The reasons for their disease are unclear.