Dec. 17--In laboratories locally and across the country, pharmaceutical companies are attempting to build a better mousetrap. That mousetrap is a new treatment for Alzheimer's disease, a debilitating illness that gradually robs patients of their ability to think, walk and reason.

In Winston-Salem, Targacept Inc. is developing a drug targeting receptors in the brain, hoping to reduce the disease's symptoms, for example. In High Point, TransTech Pharma is developing a treatment targeting the buildup of a specific protein to possibly prevent the illness.

Their research is part of an accelerating race to find a better way to treat Alzheimer's patients. Existing treatments can often be inadequate or fail to treat symptoms for very long. Companies trying to develop better medications could be treading into unfamiliar -- but possibly lucrative -- waters, health-care experts said.

"There's no such thing as a cheaper, generic treatment to prevent memory loss or reverse memory loss," said Dr. Jeff Williamson, the director of the Kulynych Center for Memory and Cognition at Wake Forest University Baptist Medical Center.

"A company that could find a drug in this area really would have no competition."

Alzheimer's disease is a progressive brain disorder that gradually destroys a patient's memory, cognitive function and communication skills. It has no cure and can cause death. Elderly people are the most vulnerable to the disease.

For caregivers of Alzheimer's patients, the disease can also be devastating. Patients can exhibit mood swings, extreme changes in personality, loss of motor function and decreased judgment. Those with advanced Alzheimer's usually need round-the-clock care. Nearly 5 million Americans have the disease, or some form of it.

Kathy Hatfield of Pfafftown knows firsthand about the effects of Alzheimer's. Hatfield's 78-year old father, Lyman, was found to have the illness about two years ago. He suffers from huge holes in his memory and can no longer remember things occurring just moments ago.

When her father was first diagnosed, "Originally, it was a death sentence for me," she said. "I was thinking 'How am I ever going to be able to stand this?'" For Hatfield, dealing with her father is a delicate negotiation. She has learned not to anger him, to try to stimulate his thinking and to encourage his daily routine.

She has disconnected the battery of her father's car to prevent him from driving, she said.

"The main, important thing with a person with Alzheimer's, in my opinion, is to continue to encourage their dignity," she said.

Such companies as Targacept and TransTech Pharma are trying to develop drugs for patients like Hatfield's father.

The companies have both reached advanced, phase-two clinical trials of their most promising Alzheimer's drugs. Most drugs go through three phases of clinical testing before the Food and Drug Administration decides whether the drug will be approved for the market. The FDA also monitors the process at each phase of a drug's development.

The market to create a better Alzheimer's drug is wide open, largely because current drugs treat only ease the disease's symptoms, and many can have side effects.

Pharmaceutical companies that are developing Alzheimer's treatments are also aiming for a piece of a large financial pie. About $100 billion is spent in the United States on Alzheimer's care annually. Even a small slice of that pie is substantial.

Kathy Hatfield's father takes Aricept and a drug called Namenda.

But creating a better treatment is not easy.

Doctors are still uncertain as to what causes the illness. To build a better treatment, doctors will have to attack the degeneration of cells thought responsible for the disease, experts said.

"The exciting thing right now is that there's a lot of technology out there," said Dr. Kevin Schulman, the director of the center for clinical and genetic economics at Duke University Medical Center.

Despite the challenges, the area's two biotechnology companies seem to be in the forefront of developing a treatment.

Targacept, which went public last April, and TransTech Pharma, a private company, have each joined with pharmaceutical giants to develop treatments for the disease.

Targacept entered a $300 million collaboration with AstraZeneca PLC last year, and TransTech Pharma signed a $155 million collaboration with Pfizer, Inc., in September to develop an Alzheimer's treatment.

Now, they need to successfully bring those treatments to market, experts said. "It's important to look over your shoulder and see how other people are doing, but it's equally important to go with your product," Schulman said.

Treating the disease Physicians and scientists have not determined the exact cause of the disease, but they widely believe that Alzheimer's is caused by the build up of certain proteins in the brain. The proteins, called beta amyloid proteins, can damage nerve cells that are responsible for transmitting signals throughout the brain.

The damage to the brain's nerve cells has serious side effects. In many cases, the cells are unable to produce enough of a much-needed chemical called acetylcholine, which plays a key role in memory and judgment. Acetylcholine helps transmit information to other cells.

Most Alzheimer's research involves inhibiting the breakdown of acetylcholine, allowing the brain to transmit information.

The race to develop a better treatment for Alzheimer's disease took off about 10 years ago, just after the country's most widely used Alzheimer's treatment hit the market.

In 1996, the federal government approved the use of Aricept to treat the disease. Aricept is made by Pfizer and works by inhibiting the breakdown of acetylcholine.

Other Alzheimer's treatments perform similar functions -- but no drug is able to repair or prevent the basic cell degeneration believed responsible for the disease. In addition, Aricept and similar drugs can have side effects including nausea, vomiting, fatigue and even anorexia.

Now, 10 years later, that earlier research has set off a wider search to develop a better drug.

Targacept, for example, is developing a drug with the working name of TC-1734. The drug works by triggering certain receptor cells in the brain to release more acetylcholine, the chemical that helps transmit information. The drug would reduce the cognitive- impairment symptoms of the illness. It also seems to have fewer side effects than medications like Aricept, according to the company's studies.

Targacept, based in the Piedmont Triad Research Park, has about 75 employees. It is developing drugs based on nicotine research to treat diseases of the central nervous system, which also include schizophrenia and cognitive impairment.

The company entered the public market in April. Its Nasdaq stock price debuted at $9 a share but has since ranged from $5.26 to $9 a share, reflecting the volatile biotechnology industry.

Targacept officials are betting that their particular drug will deliver positive benefits.

"The problem right now is there's a huge unmet need," in helpful Alzheimer's treatments, said Alan Musso, Targacept's chief financial officer. "It's just an area, right now, where the current therapeutics that are available aren't very effective."

The pharmaceutical industry is taking keen interest in the small company's research. AstraZeneca, Targacept's partner in the Alzheimer's research, makes the popular acid-reflux medications Prilosec and Nexium, for example.

Generally in developing drugs for the disease, "the failure rate is going to be high, but the reward is going to be higher," said Don deBethizy, Targacept's chief executive.

TransTech Pharma is taking a different route.

The company, which has about 80 employees, is using specific molecules to try to prevent Alzheimer's in patients, rather than treat the symptoms of the disease.

The company is developing molecules that could help prevent the buildup of the beta amyloid proteins believed responsible for the illness, TransTech Pharma officials said. Beta amyloid proteins can eventually kill healthy nerve cells in the brain, causing the debilitating symptoms common to Alzheimer's.

A steadily aging population has made the need for drugs treating Alzheimer's disease and age-associated memory illnesses more vital, experts said.

"There's a demographic tsunami coming our way, in terms of Alzheimer's disease," said Dr. Anton Porsteinsson, an assistant professor of psychiatry at the University of Rochester School of Medicine in New York. "It's a big problem today, and it's going to be a huge problem."

TransTech Pharma officials agreed. "The company that comes up with a drug that really does treat this is going to be viewed as a real savior out there," said Stephen Holcombe, the company's chief financial officer. "It's certainly a popular illness to go after."

A local industry The focus on Alzheimer's treatment is one of the clearest examples of the region's attempt to transition into a new industry, economic-development officials said. An increasing focus on biotechnology and health care is one way to shift this area's economy away from its tobacco and manufacturing past, they said.

Winston-Salem has worked to lure doctors and scientists from such places as Harvard University, for example.

Targacept and TransTech Pharma aren't the only two North Carolina companies that are developing Alzheimer's treatments.

Voyager Pharmaceutical Co. in Research Triangle Park and Merz Pharmaceuticals, a German company with an office in Greensboro, are also developing Alzheimer's drugs.

Within the health-care industry, there's a sense that some of the major work on Alzheimer's is being performed locally. Many of the other possible treatments for the illness are still in early testing stages, for example.

But designing complicated new medical treatments for the elderly is far from easy.

Most small biotechnology companies fail, particularly when their products are tested in humans. The pressure will be on for companies to produce positive results for their investors, said Schulman, the Duke professor.

Still, Schulman said that the time is right for companies to explore new treatments for age-old illnesses.

"Biotechnology is the industry of huge risk," Schulman said. But "the exciting thing right now is that there's a lot of technology. There's at least the promise that we have new approaches to things that haven't been reachable before."

Where is Alzheimer's research headed? Some experts say they think that companies will follow TransTech Pharma and attempt to develop drugs that will prevent the disease.

Alzheimer's "is probably kind of settling in and taking hold of your brain for possibly decades before you develop clinical symptoms," said Porteinsson, the University of Rochester doctor. "We do believe that, in the long run, the treatment of Alzheimer's disease will have to be preventative."

Such drugs as Targacept's medications could provide stronger treatments for the symptoms of Alzheimer's, as well as help treat other disorders of the central nervous system, but "basically, the targeting of the underpinning of the disease is, in my mind, the future," Porteinsson said.

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