Source: New York Times
Date: July 29 2003

Race Is On for a Pill to Save the Memory


the race for smart drugs

They are called smart pills or brain boosters or, to use the preferred pharmaceutical term, cognitive enhancers.

But whatever the name given to compounds created to prevent or treat memory loss, drug companies and supplement producers - eager to meet the demands of a rapidly growing market 0 are scrambling to exploit what they view as an enormous medical and economic opportunity.

Three drugs being prescribed for Alzheimer's disease - donepezil (Aricept), galantamine (Reminyl) and rivastigmine (Exelon) - have been shown to delay somewhat the loss of mental abilities in people with the illness. So has the drug memantine, which has been used for years in Europe but has not been approved in the United States. Some experts also say that performing mental exercises and adding fish oil to the diet can delay memory decline.

Pharmaceutical companies are investigating dozens of other compounds to see whether they can help people who have memory difficulties but have not progressed to Alzheimer's. Some researchers hope that drugs will eventually prevent the deficits that even healthy elderly people experience.

Much of the excitement among pharmaceutical companies, which have dozens of drugs in development, stems from advances in clarifying some of the brain processes and biochemical pathways that can hinder or help memory storage and retrieval, said Dr. Paul R. Solomon, a professor of psychology at Williams College.

"The basic research into the causes of memory disorders is going very rapidly," said Dr. Solomon, who is also co-director of the Memory Clinic at the Southwestern Vermont Medical Center in Bennington.

But it will probably be at least five years before any of those drugs meet the standards for approval by the Food and Drug Administration, researchers said.

Clearly, the market for memory enhancers is growing with the aging of the population.

Dr. Steven T. DeKosky, a professor of neurology and psychiatry at the University of Pittsburgh School of Medicine, says he has noticed a marked increase in anxiety among baby boomers, who are watching their parents descend into Alzheimer's and hoping that new medicines will help them avoid the same fate.

"People in their 40's and 50's are saying: `How can you help my mother? And, by the way, how can I avoid this?' " Dr. DeKosky said. "Ten years ago, people wanted to know how frequently they should have their blood pressure checked and what sorts of food they should eat. Nobody ever asked what they should be doing to prevent themselves from getting a late-life dementia."

Even among those who are already suffering memory loss, Alzheimer's is far from the only source. An estimated four million Americans have it, but millions more suffer from other disorders that can lead to dementia, including Parkinson's disease, multiple sclerosis, stroke, head trauma and schizophrenia.

Experts estimate that an additional four million people have a syndrome called mild cognitive impairment, which may progress to Alzheimer's. People with the impairment can function on their own but have gaps in their memories.

Economic imperatives are also driving the search for new and better treatments for memory disorders.

The current cost of Alzheimer's alone runs $100 billion or more, said Dr. William Thies, vice president for medical and scientific affairs of the Alzheimer's Association, a research and support group.

If no new medications for memory disorders are found, Dr. Thies added, the number of Alzheimer's patients could quadruple by midcentury.

"That's going to bankrupt our health care system," he said. "So there's a need to find a way to short-circuit that impending disaster."

Except for extreme cases like advanced Alzheimer's, memory disorders do not generally disrupt what is often called procedural memory, the ability to perform basic tasks or motor skills like riding a bicycle or getting dressed.

Far more vulnerable is episodic memory, the ability to recall specific information about people, dates and events. Many of the new compounds being scrutinized seek to improve the way recent memories are stored, transformed into long-term memories and brought back into consciousness when needed.

Drugs approved specifically for Alzheimer's are being tested in patients who have mild cognitive impairment. But the medications can have side effects like nausea and diarrhea. So researchers are looking ahead to the second generation of memory enhancers, some of them now in clinical trials.

Some of the drug companies most involved in the search are small enterprises, focused on specific pathways or aspects of brain biochemistry. Memory Pharmaceuticals in Montvale, N.J., is developing compounds that maintain brain levels of a substance called cyclic AMP, which transmits intracellular signals and has been shown in mice to play a role in memory formation and retrieval.

Another company, Cortex Pharmaceuticals in Irvine, Calif., has two drugs in clinical trials that bind themselves to sites on nerve cells called AMPA receptors. The receptors respond to signals between cells carried by the neurotransmitter glutamate, and the drugs, called ampakines, are intended to enhance the strength of the incoming signal.

"It's like an amplifier to a stereo set, and you can turn up the volume of brain activity quite a bit by using these compounds," said Dr. Roger Stoll, president, chief executive and chairman of Cortex.

Despite optimism among neuroscientists about eventual success, few expect memory enhancers to be a panacea. Many researchers acknowledge that even if they find effective treatments, there is no guarantee that the drugs will do anything for people who age normally.

There is even less optimism that these drugs will boost the brain power of younger people hoping to master a foreign language or excel on a calculus examination.

Although some drugs have clearly enhanced the ability of animals to learn and perform routine tasks, that does not necessarily mean the same medications will help people remember names and faces, said Dr. Rodney Pearlman, president and chief executive of Saegis Pharmaceuticals in Half Moon Bay, Calif.

"It isn't clear that animals use the same kinds of memories that humans do," said Dr. Pearlman, whose company is developing several memory enhancers. "A mouse doesn't have to remember a PIN number to get along during the day."

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