Sept. 29, 2008— -- As medical disorders go, narcolepsy has the paradox of being popularly portrayed in comedy, but being a rare, devastating and poorly understood condition in real life.
Only one in 2,000 people have the disease, which means doctors can rarely get enough patients or funding to really study narcolepsy and make advances to treat it. But Sunday, in the journal Nature Genetics, researchers reported that they discovered a genetic variant which increases a person's susceptibility to narcolepsy by 79 percent.
Dr. Emmanuel Mignot, a co-author of the study, said the gene discovery is not a breakthrough for a cure -- only one in 300 people with the variant actually have narcolepsy -- but a big step toward understanding how this extraordinarily rare disease works.
"It's definitely a very exciting finding ... and there is more to come," said Mignot, who is professor of Psychiatry and Behavioral Sciences and director of the Center for Narcolepsy at Stanford University.
For some narcolepsy patients, any news, no matter how buried or complicated to understand, is big news.
After Sharon Smith lost her career and her independence to narcolepsy in 1989, she said she kept an eye on any narcolepsy news.
"It would be wonderful if they could predict, even a percentage of people destined to have narcolepsy," said Smith, president of the Board of Trustees at the Narcolepsy Network Inc in North Kingstown, R.I.
"If we can't be cured, the next best thing is to be certain that future generations don't have to suffer," Smith said.
A Career Ruined by Narcolepsy
Sharon Smith's narcolepsy symptoms came to a terrifying head one night as she walking home from her job as a senior tax manager at the Arthur Andersen accounting firm in Manhattan. Before her collapse, Smith had no idea that she had narcolepsy.
"I was walking to Penn station, and some people stopped me, I guess they were tourists, and asked for directions," Smith said. "I thought to myself, 'I really should have warned them that Central Park isn't the best place in the dark.'"
The next thing she knew, Smith was lying paralyzed against a shoe store unable to stop someone from robbing or hurting her.
"It was very scary," she recalled. "I was very disappointed by the people in the shore store; they saw it and did nothing to help."
Luckily two ladies passing by stopped and stayed with her, thinking she had a seizure. Ten to 15 seconds later, she was back on her feet.
"That was good, that was reassuring because the fear can cause the attacks to come back," Smith said.
For Smith, that small worry over the tourists started a severe reaction among some narcoleptics called cataplexy -- a sudden loss of muscle control set off by a strong emotion.
She had more benign symptoms before as a child, but not a full body collapse.
"When I laughed very heartily, my hands would go dead -- I couldn't even pick up a pencil," said Smith. "It used to be a joke in my family."
But by age 31, Smith's narcolepsy had progressed to a debilitating point. She couldn't sleep at night, but she couldn't stay awake enough to work during the day. Her cataplexy became a full body collapse even at the surprise when her mail was delivered early.
"A lot of things went through my head at the time, I was thinking brain tumor, brain cancer, multiple sclerosis," Smith said. "Narcolepsy was the furthest thing from my mind."
Within a year after her diagnosis, Smith left her career.
Dealing With the Drugs Difficult, Too
"Untreated, even crossing the street is a challenge," Smith said. "If the light changes to yellow, you worry, 'Am I going to get across?,' and that can cause cataplexy."
Drugs helped, but Smith decided to stop using the high doses of antidepressants that mitigate the narcolepsy symptoms when she got pregnant with her second child. Even today, the drug treatments for narcoleptics are rife with side effects.
"It's brute force. It's hitting them over the head with medicine to manage it," said David Carley, Medicine and Pharmacology director at the Center for Narcolepsy, Sleep and Health Research at the University of Illinois at Chicago.
"Basically we're at the point of saying, 'OK, I know you tend to fall asleep. I'm going to overcome that by just bulldozing your central nervous system,'" Carley said.
Narcolepsy specialists borrow drugs made for other medical conditions that happen to take over the body's sleep cues, Carley said. With narcolepsy, the person doesn't sleep more, but just sporadically and suddenly.
Animal testing has started to explain aspects of narcolepsy, but even with treatment, many patients still suffer from debilitating exhaustion trying to fit with society's work days.
"In humans it's not a genetic mutation that causes narcolepsy," said Mignot, the director of the Center for Narcolepsy at Stanford. "It's an autoimmune response."
Narcolepsy researchers, actually at Mignot's lab, discovered the immune response explanation only eight years ago. They found that, somehow, the body was destroying nerve cells in the brain responsible for creating a chemical called hypocretin involved in sleep. By the time someone develops narcolepsy symptoms, 90 percent of the nerve cells n their brain that can create hypocretin are gone.
"But we still don't it understand it very well," Mignot said. "That's why it's very important to look for all the genes, so we know how these genes are involved in the immune response."
While the new genetic link to narcolepsy may help doctors to understand how the disorder develops, and therefore make better drugs to treat it, researchers do not expect that it will help diagnose patients -- and diagnosis is a serious problem.
More Understanding Needed
"A lot of the past clinical studies suggest that it's about six to seven years from the onset of symptoms to an actual diagnosis," said Dr. James Herdegen, medical director of the Sleep Science Center at the University of Illinois at Chicago.
During those six to seven years, Smith said many patients slowly lose control of their life, their jobs and their families.
"Without treatment, I would be confined to my house," she said. "I could not do anything or commit to anything at a particular time. I could accomplish things but not on anybody's schedule but my own."
"As a mother, it's a challenge to care for your children if you're not treated," said Smith.
While she is waiting for better treatment and early diagnosis for others with narcolepsy, Smith hopes to raise awareness in the public.
"The most important thing to a person with narcolepsy is to be around people who can understand and won't berate them," Smith said. "Employers, by and large, they don't want to have a person with narcolepsy on the payroll."
Smith said it is common to come across people diagnosed with narcolepsy whose families still believe they're just lazy. "They'll say, 'Oh, you need vitamins,' or 'You just need more motivation.'"
Smith is just looking for more hypocretin.