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David Baxter PhD

Late Founder
Drugs Could Help Healthy People Boost Brainpower
August 12, 2004
Tulsa World

You can rub Rogaine into your scalp to try to regain the hairline of your youth. You can inject Botox into your forehead to smooth time's inroads, at least temporarily. And, some scientists predict, you'll eventually be able to pop a pill to freshen up the inside of your head, as well.

Thanks to recent strides in understanding how the brain works, it's only a matter of time before medications specifically designed to improve mental ability, or cognition, hit the market.

"The hallmark of these drugs is they don't create more memory," says John Tallman, CEO of Helicon Therapeutics of Farmingdale, N.Y., which plans to begin testing its most promising brain drug in humans later this year. "What these drugs really do is enhance the conversion process of short-term to long-term memories."

Besides Helicon (for the mountain in Greek mythology where Apollo played with the Muses), companies with such evocative names as Sention (apparently a play on sentient, which means conscious or aware) and Memory Pharmaceuticals are focusing on medications to treat patients whose brains are impaired by disease or injury.

But the real market for such drugs might be healthy people who would simply like to be a little quicker on the uptake.

Americans already spend $1 billion a year on dietary supplements claiming to boost brainpower, even though there's little evidence that they work, notes an article in the May issue of Nature Reviews Neuroscience. From vitamin B12 to ginkgo biloba to "BrainQUICKEN" capsules -- "used by top students at every Ivy League institution," according to the product's Web site -- health-food stores and the Internet are rife with products promising to enhance memory and learning.

Once the Food and Drug Administration allows a drug on the market to treat, say, Alzheimer's disease, doctors could prescribe it "off- label" for any purpose they like, including sharpening healthy minds dulled by age or fatigue. And Internet shoppers would have their pick of Web sites selling the drugs without even requiring a prescription.

To an extent, it's already happening. Though it's not clear how widespread the practice is, high school and college students who don't have attention deficit-hyperactivity disorder are taking Ritalin to help cram for exams. Scientists have been known to pop Provigil, approved only to treat narcolepsy, to increase alertness before speaking at professional meetings.

"People are already using a wide range of medical drugs to improve their own performance," says Sention CEO Randall Carpenter, citing Viagra's popularity with men who don't have erectile dysfunction as one example. "It's almost impossible to stop people if they want to do that."

On its Web site, Memory Pharmaceuticals of Montvale, N.J., acknowledges that the potential market for its compounds, one of which is being tested in humans, might extend far beyond patients with Alzheimer's and other memory-robbing ailments. Though 37 million people worldwide have Alzheimer's disease, the company says, more than 180 million -- or half of all people over 65 -- are experiencing "age-associated cognitive decline."

"This decline is not clearly linked to a definable disease condition and may be a 'normal' part of the process," the company says on its Web site.

Memory Pharmaceuticals raised $35.4 million in its initial public offering this year. President and chief science officer Axel Unterbeck says the medical need alone "would be worth the entire investment" in developing drugs to improve cognition. But he acknowledges that healthy people will seek them out. "This indeed will be a very interesting trend to look at," he says.

Tallman says older people are "very, very concerned about their memories, because their memories are what make them human. No honest person would ever say to you, 'I would never take the drugs.' "

Still, there's no guarantee drugs that work in people impaired by disease also would benefit healthy people who would simply like to recall names more quickly.

For example, first-generation Alzheimer's drugs Cognex and Arricept block the breakdown of acetylcholine, one type of neurotransmitter, a substance that enables nerve cells to communicate with each other. Alzheimer's patients' have a shortage of acetylcholine, but people with normal brains do not, so it's not clear what effect the drugs would have on them, says Steven Rose, a director of the Brain and Behavioural Research Group at the Open University in England.

And even if such drugs did enhance cognition in average individuals, Tallman says, "highly functioning people would have probably limited benefit."

Duke University researchers have found that the nicotine patch, approved only to help smokers break the habit, boosts brain function in people with mild to moderate Alzheimer's disease and adults with ADHD and schizophrenia. But earlier tests in healthy volunteers found only a modest effect, says Edward Levin, a professor in Duke's psychiatry and behavioral science department.

Even in Alzheimer's patients, Levin cautions, the nicotine patch's benefits aren't worth the risks. Side effects include an elevated heart rate and blood pressure, sleep disturbances, nausea and dizziness.

The nicotine patch points out another obstacle toward developing "smart drugs" for normal brains. "It has to be as safe as water," Carpenter says. "That's a very daunting task that few people want to try to accomplish."

"The issue is: How do you specifically alter such a complex organ as the brain without affecting anything else?" asks biologist Robert Gerlai, a memory researcher at the University of Hawaii. "The brain doesn't just work on learning and memory. It has all kinds of other functions."

Just who should get a boost?

James McGaugh, director of the Center for the Neurobiology of Learning and Memory at the University of California-Irvine, bristles at the notion of people with normal brains taking medication to boost brainpower. After all, he says, no one regards the slowing down of the body with age as a medical condition.

"Does Michael Jordan have age-related physical impairment?" McGaugh asks. Just as Jordan may not be as agile on the basketball court as he used to be, McGaugh says, there's strong evidence that memory processing slows with age. Any middle-aged person who has grasped for a word or a name can vouch for that. But "it's only critical if you want to appear on "Jeopardy!," McGaugh says.

Things get even more complicated if one considers the possibility of enhancing memory and learning in young people, McGaugh says.

For example, he says, if doctors took such a drug throughout their training, would they be required to continue taking it as a condition of their license to practice medicine? And what about children? McGaugh asks. "Are you going to put the pill in their lunchbox when they go off to school?" And, he asks, what if you can't afford to?

Nature Reviews Neuroscience published an article about the ethics of enhancing mental performance. The authors, a panel of neuroscientists and ethicists, suggest that "when we improve our productivity by taking a pill, we might also be undermining the value and dignity of hard work, medicalizing human effort" and labeling a normal attention span abnormal.

But researcher Mark Bear, a Massachusetts Institute of Technology neuroscientist, says it's unlikely that brain-boosting drugs will have much effect on young, healthy individuals whose brains have not yet begun to slow down.

"I think it's pretty clear in animal studies that treatments that will enhance memory in aged rats often will fail in young rats," says Bear, co-founder of Sention, a Providence, R.I., company that is testing two experimental drugs for Alzheimer's and other memory- robbing ailments in volunteers.

To Bear, taking a drug to counteract aging's effect on the brain isn't much different from wearing bifocals to compensate for aging vision.

Or maybe "smart drugs" are more analogous to Botox than to bifocals, another example of "the baby-boom generation wanting to maintain a youthful quality of life right into old age," says Bear, who, at 46, falls smack-dab in the middle of the boomer generation. "We really are not accepting age gracefully."
 
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