On the front lines

ON THE FRONT LINES: Neil Buckholtz, left, of the National Institute on Aging says researchers “just have to try these various approaches. It’s very time consuming, very expensive.” David Bennett of the Rush Alzheimer’s Disease Center conducted one of the first long-term studies of the disease. (National Institute on Aging / Rush University Medical Center)

On a warm autumn afternoon, toward the end of a daylong barrage of PowerPoint presentations, a white-haired, gentlemanly fellow named Michael Merzenich faced a room full of neuroscientists and pharmaceutical executives and declared that, really, they could all pack up and go home. He thought he could stop Alzheimer's disease by doing nothing more than sitting old people down for a few months in front of computer screens and retraining their brains.

What was odd about Merzenich's pronouncement was that it hardly seemed odd at all. He had been preceded to the stage -- and was followed the next day -- by a procession of researchers who offered widely variant prescriptions for confronting the disease, many as complicated as Merzenich's was comparatively simple.

The scientists blamed Alzheimer's on misfolded proteins, broken neural pathways, misprinted gene maps, everything, it seemed, but the stage of the moon. Here and elsewhere for years they have laid plans to fight the disease with all of the Big Pharma firepower they could muster. But they also talked about inhaling insulin, eating turmeric, fixing vitamin deficiencies, injecting stem cells and inventing neuro-protective vaccines. They couldn't all have been talking about the same disease, could they?

A month after San Francisco, at another conference (this time in New York), some of the same participants delivered much of the same data, but with yet more novel approaches piled on. A month later, the road show moved on to San Diego, where even more alternate explanations were added to the roll.

As with Merzenich, when someone stands in front of a crowd of excessively bright and dedicated scientists and delivers a theory radically different from what everyone else in the room has been saying, nobody blinks. Or even seems to notice. It wasn't that the other scientists thought Merzenich was wrong or right or crazy. He is a highly respected neuroscientist. In Alzheimer's research, lots of people seemed to have quit believing anything is wrong or right or crazy. Mainly, they shrug.

Surveying the ideas proposed at the New York meeting, Grant Krafft, chairman of Acumen Pharmaceuticals Inc. of South San Francisco, shook his head and sighed. "There was a lot of mucked-up science here today," he said.

There are currently five medications approved for treatment of Alzheimer's in the United States, one of which causes severe problems and is rarely prescribed. The other four take in an estimated $4 billion a year. They do nothing to stop the disease and have only marginal, often transitory effects on its symptoms. They're on sale because there is little else to offer people afflicted with the mind-crippling disease.

There are 56 more drugs in some stage of the clinical trials regulated by the Food and Drug Administration; few people other than their creators have great hopes they will work. Sometimes, not even the creators are optimistic.

Wyeth, a New Jersey-based pharmaceutical company, has 10 candidate Alzheimer's drugs in clinical trials. Drug companies have had such difficulty translating their research into effective neural disease treatments that Wyeth has decided to push everything it had into trials and see what, if anything, worked. Internally, Wyeth calls this the "fail faster" approach.

Neil Buckholtz, chief of the dementias of aging branch of the National Institute on Aging, said the pharmaceutical industry had little choice. "This is basically a 'throw the spaghetti against the wall' strategy. . . . We just have to try these various approaches. It's very time consuming, very expensive, but it's the only way we'll know if things work or not."

Spaghetti or not, after listening to scientists discussing Alzheimer's and how to fix it, it is hard to come to any conclusion but that, at least for the moment, the Alzheimer's endeavor is a mess.

What's at stake

The individual devastations of Alzheimer's disease are by now well known. It is one of several, and by far the most common, of so-called neurodegenerative diseases; literally, diseases that destroy the brain.

Alzheimer's first afflicts the areas where new memories are encoded. Early symptoms include the incidental episodes of forgetfulness often brushed off as "senior moments." The symptoms progress, slowly at first, to more frequent memory disruptions, to broader cognitive problems -- confusion, disorganization, disorientation. Eventually, as the disease works its way through more areas of the brain, it alters personality and destroys the self, reducing the victim to little more than a warm body greatly in need of care.

An estimated 5 million Americans have Alzheimer's. That number has lately been growing exponentially; ironically, as medical care improves and people live longer every decade, it will continue to do so.

By 2010, Alzheimer's care will cost Medicare about $160 billion a year. By 2035, it could overtake the defense budget. One analysis has estimated that by 2050, Alzheimer's will cost Medicare more than $1 trillion annually. Those numbers do not include privately insured and uninsured costs.

"From a social and economic view, it is about the money, the growing diversion of resources to sustain life in those increasingly unaware of their own lives," Harry Tracy wrote recently in NeuroInvestment, his industry newsletter. "There is no greater public health issue looming in the developed world."

While the cost of Alzheimer's soars, federal money spent on research has flattened and is expected to decline in real terms in the future as the competition for federal money heightens. The rising costs of treating the disease coupled with reduced research funding is, to some, a foreboding combination.

Andy Grove, the former chairman of Intel Corp., spoke at this year's Society for Neuroscience convention in San Diego. Grove, who has Parkinson's disease, lamented the lack of a full-scale attack on neurodegenerative disorders: "We are about to experience an explosion of Alzheimer's disease cases. . . . This situation is best compared to astronomers following a meteor hurdling toward San Diego, aimed to hit a very precisely calculated place and time. What would we do if we had such a situation? I think we would take it a little more seriously than we take the economic meteor that's coming just as predictably our way."