Smart pills’ make headway

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.
Someday soon, if someone jokingly asks you if you remembered to take your smart pill, you can answer yes — seriously.

By Rita Rubin, USA TODAY

http://www.usatoday.com/news/health/2004-07-07-smart-pills-main_x.htm

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. (Related story: Who should getting a boost in brainpower?)

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."

‘Normal’ cognitive decline

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 would also 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."

Perhaps somewhat surprisingly, Stanford University researchers found that nicotine gum as well as Aricept, used to treat patients with mild to moderate Alzheimer’s, did improve healthy, middle-aged pilots’ performance in flight simulators. However, Aricept also can cause side effects that would be pretty undesirable in a pilot, such as dizziness, fainting and vomiting, says pharmacologist Martin Mumenthaler, who led the study.

"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." In addition, Gerlai and others in the field point out, there is the potential risk that memory-enhancing drugs would work too well, preventing users’ brains from distinguishing between important and trivial information.

Some scientists say Helicon’s leading drug, aimed at activating a protein involved in the formation of long-term memories, might interfere with short-term memory, Tallman acknowledges.

Animal "memory models are pretty good, but it’s hard to really get a total read on human memory without doing human trials," he says. Although Helicon has not yet begun testing its drug in people, Tallman says he suspects that any adverse effects on memory would be transient.

A mental ‘jump-start’

Phase I trials, designed to assess the safety of experimental drugs, are conducted in healthy volunteers. So besides monitoring the volunteers for side effects, Sention, of Providence, and Memory Pharmaceuticals are administering tests to assess their drugs’ effects on learning and memory.

Mark Bear, a Massachusetts Institute of Technology neuroscientist and Sention co-founder, emphasizes that the Phase I studies were too small to yield robust data about the drugs’ effectiveness. Still, he says, "I would be willing to say that the results were very encouraging."

Though it would be unethical for Bear, 46, to test his company’s drugs on himself, he does occasionally partake of a medication that might be the first safe and effective smart drug on the market.

Modafinil, sold as Provigil, was approved in 1999 for the treatment of daytime sleepiness in narcolepsy patients. It’s not cheap. Web sites sell 30 100-milligram tablets for around $200.

In a small study of healthy men published last year, Barbara Sahakian of the University of Cambridge found that modafinil safely improved performance on tests of memory and attention.

Sahakian says she and her collaborators limited their study to men to eliminate the potentially confounding effect of women’s menstrual cycles. But, she says, there’s no reason to think that modafinil wouldn’t work the same in women.

"It’s probably the first smart drug that I’ve seen," says Sahakian, one of the co-authors of the Nature Reviews article on cognitive enhancers.

Bear says he takes modafinil "to jump-start myself across time zones," not to enhance his mental performance.

He first asked his doctor for a prescription before traveling to a scientific meeting in India. "I had to arrive and give a seminar in the same day. I said to my doctor, ‘Look, I’m going halfway around the world. I simply would not be able to function’ " without the drug.

Though Bear took modafinil to keep from nodding off in the middle of his presentation, he acknowledges that "anything that increases alertness will increase cognition."

And anyone who has downed a double espresso — or two or three — while studying for an exam or writing a report would probably drink to that.