Thursday, February 18, 1999

Researchers Find Gene,
Are Optimistic for Cure



H
untington's disease is an incurable progressive neurological disorder that afflicts all aspects of the mind and body.

The cause
Extensive death of neurons in the basal ganglia, a region of the brain that controls movement and possibly cognition, is the result of the disease. Other affected areas:

  • Caudate nucleus: An area involved in motor control shows severe shrinkage in the victims of the disease.

  • Putamen: Also involved in motor control is affected in advanced cases.

SOURCES: Chicago Tribune, AMA
Encyclopedia of Medicine and news reports

By Norma Wagner

Researchers discovered the renegade gene that causes Huntington's disease on chromosome 4 in 1993.

Huntington's disease results from a genetic "stutter," an explosive reproduction of one tiny bit of genetic information.

Scientists believe a protein produced by the mutated gene slowly destroys brain cells, resulting in progressive mental and physical impairment. They are trying to discern how the mutated HD gene destroys specific brain cells and are researching ways to rescue a dying cell through the use of drugs.

They still don't know what the normal version of the gene does.

Because the gene for Huntington's is dominant, it is passed on to children 50 percent of the time.

Symptoms usually begin between ages 35 and 40, but it also has been diagnosed in patients as old as 80 and in children as young as 3. "That is rare," said Debra Lovecky, of the Huntington's Disease Society of America, "but we have enough of them to call it Juvenile HD."

Symptoms are subtle at first, with occasional body spasms and personality changes. As the disease progresses, patients get easily irritated or excited. They may start behaving irresponsibly, wander aimlessly or lose control over their impulses.

As more brain cells die over years or decades, patients may lose their memory or ability to think rationally. Some become violent, others withdrawn. Severe depression can lead to suicidal behavior.

In the final stages, almost all functions become impaired and abnormal movements involve the entire body to the point where eating, drinking and sitting still become nearly impossible. At that point, patients need full-time care.

Death, most often from choking, pneumonia or a fall, occurs an average of 15 years after the onset of symptoms. Although drugs can relieve emotional and physical symptoms throughout various stages of the disease, there is no cure.

"The typical approach, at least from a psychiatric point of view, is to treat psychiatric symptoms," said Michael Smith, Amy Bishop's psychiatrist and an assistant professor at the University of Utah. "If someone is having trouble with depression, they'll be on an anti-depressant. And anti-psychotic drugs . . . can help minimize or diminish the excessive or uncoordinated movements. But it's not fully effective."

And what works for one patient may not necessarily work for someone else, he added. "There's no magic recipe for all this." Bishop, for example, takes four medications regularly for depression and psychosis, or delusions. "Her thinking is mixed up and disorganized and vacant most of the time," Smith said.

The good news: HD results from a simple gene mutation, he said. "So I expect that sometime within the next 10 years we'll have some ability to intervene at the genetic level and maybe stop the disease, though I don't know that we'll be able to reverse it once it's started.

"The future in all of the mental illnesses is brighter than the past. Our ability to treat things is not as robust as we'd like, but we'll get better with time. I expect in the course of my career I'll be able to diagnose this illness [HD] and say `That's the bad news, but the good news is we can stop this.'

"I don't think that's overly optimistic."