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(Page B-2 )

Queuing up hope for Q-10 | Parkinson's study looks at
coenzyme to retard disease


Cheryl Clark
STAFF WRITER

18-Jan-1999 Monday

A dietary supplement sold in health food stores is the subject of a $2
million federal grant to a UCSD researcher who thinks high doses of a
purified form of the substance might keep patients in the early stages of
Parkinson's disease from getting a lot worse.

"Our hope is that we might be able to slow the progression, and someone who
had the disease for 10 years would function as if they'd only had it for
five," said Dr. Clifford Shults, UCSD professor of neurosciences and
principal investigator of the study. "Their mobility would be better, and
their response to medication better, too."

The supplement, Coenzyme Q-10, occurs naturally in mitochondria, the
so-called power plants that generate energy in cells.

For more than 15 years, small doses have been synthesized in pill form and
sold over the counter in health food stores and drugstores as an
anti-oxidant and free-radical fighter, in hope that it can fight heart
disease and cancer, although no studies have proved that it can.

A bottle of 120 tablets of 30 milligrams each can cost between $15 and $40,
and officials say its sales have slowly grown over the years.

In patients with Parkinson's disease, mitochondrial function is impaired,
leading to the decline and death of nerve cells that produce dopamine, a
neurotransmitter lacking in patients with Parkinson's disease, researchers
have found. Lack of dopamine leads to the tremors and stiffness that
characterize Parkinson's.

In 1997, Shults and fellow UCSD neuroscientist Dr. Richard Haas, along with
Dr. Flint Beal, chief of neurology at Cornell University School of
Medicine, measured levels of Coenzyme Q-10 in Parkinson's patients and
found them significantly lower than levels in non-patients of the same age
and sex.

Beal and Shults then tried to see if they could mimic the disease in mice.
In the 1980s, researchers discovered that MPTP, an ingredient in an
intravenous drug used by addicts, caused the same tremors and rigidity seen
in Parkinson's disease. MPTP also was found to be toxic to
dopamine-producing nerve cells.

First, Shults and Beal gave groups of mice either a standard diet or a diet
laced with Coenzyme Q-10, then followed that with MPTP. They discovered
that mice fed Coenzyme Q-10 had significantly greater levels of dopamine
than mice that were fed the standard diet alone.

If they could duplicate those results in humans with Parkinson's disease,
they just might be onto something, the researchers thought.

The question would be whether Parkinson's patients -- who sometimes have
trouble absorbing medications -- could ingest enough of the high dose
substance to make a difference.

Shults gave a variety of high dose Coenzyme Q-10 to 15 Parkinson's patients
and found no significant side effects except minor urinary changes. What is
more, the researchers found comparable increases of the substance in the
patients' blood and an increase in mitochondrial activity, the part
governed by Coenzyme Q-10.

In late 1997, Shults applied to the National Institute of Neurological
Disorders and Stroke in Bethesda, Md., the arm of the federal government
that allocates research money for Parkinson's disease. Last fall, he
received $2 million and the go-ahead to recruit 80 early stage Parkinson's
patients for a three-year study of Coenzyme Q-10.

Protective treatments

Shults, who directs San Diego's National Parkinson Foundation Center of
Excellence at University of California San Diego, said considerable
progress has been made in Parkinson's treatment. Medications such as
levodopa can control some of the symptoms, such as the resting tremors,
slowness and rigidity. A surgical procedure called pallidotomy shows
promise for people suffering from severe forms of the disease.

But nothing has been found to prevent further deterioration of nerve cells,
Shults said.

"The goal we've really started pursuing is to try to develop protective
treatments," Shults said. "Our study is the first federally sponsored one
to look at this compound in a systematic fashion."

Dr. Dee Silver, a La Jolla neurologist and medical director of the
Parkinson's Disease Information and Referral Center of San Diego County,
applauded the effort, saying, "There's a lot of basic investigative
evidence that this drug has a possibility of reducing progression."

As word spreads among patients, some are already heading to the stores to
buy the substance, Shults and Silver said.

But in Shults' study, the doses will be 10 to 40 times the amount in most
store-bought tablets, "much larger than one might be able to easily
afford," Shults said. And the amount of Coenzyme Q-10 in the experimental
doses, which Silver and others said can vary in the store-bought products,
will be much more tightly controlled.

Those enrolled will receive one of three doses, 300, 600 or 1,200
milligrams per day, or a placebo. They will be recruited at centers in Los
Angeles; Chicago; Philadelphia; Baltimore; Atlanta; Portland, Ore.; St.
Louis; Rochester, N.Y.; Kansas City, Mo.; Albany, N.Y.; West Bloomfield,
Mich.; and Charlottesville, Va.

Only patients with early stage Parkinson's will be enrolled to avoid
interference with other drugs and cell deterioration in patients with
severe diseases that could confuse results.

Shults said patients will not be recruited in San Diego, but San Diegans
may be able to participate through the University of Southern California in
Los Angeles.

Concern about hype

Shults and others worry that because only 80 patients are being recruited
and because of the potential for "holistic hype" on the Internet, other
patients will rush to buy the drug, washing down hundreds of pills a day.

"I've gotten zillions of calls from people about this, wanting to know if
it works," said Gerry Graf, Costco's five-state regional pharmacy
supervisor, who heard Coenzyme Q-10 discussed on a recent radio show about
Parkinson's disease.

"People need to understand that we don't know yet if this works or has side
effects in these high doses," Graf said. "We really have no idea. Instead
of doing a little study on their own, people could be killing themselves."

Shults echoed Graf's concern.

Kimberly Seidman, West Coast director of the National Parkinson Foundation
in Los Angeles, said patients are calling her asking questions about
Coenzyme Q-10.

"They ask if they should take it, and my response is very clearly that
there's no evidence that it can make a significant difference. We always
tell people to talk with their doctors first."

Seidman, whose late father had Parkinson's disease, has been taking small
doses of Coenzyme Q-10 herself as a precaution since she met a San Fernando
Valley physician and Parkinson's patient who took the compound after
reading that it might help his heart murmurs.

"He was pretty sick and getting ready to retire. His gait was slow and he
was stooped over," and other symptoms of Parkinson's were starting to
worsen, she said. "After he was on Coenzyme Q-10 for six months, he
dramatically improved."

While he never regained full function, he maintained an improvement for
several years, she said.

Seidman lost touch with him. But she is delighted that Coenzyme Q-10 is
being subjected to a scientific trial.

Parkinson's disease is diagnosed in 50,000 people annually in the United
States and is estimated to affect between 500,000 and 1 million people at
any time. Actor Michael J. Fox, U.S. Attorney General Janet Reno and boxer
Muhammad Ali have been diagnosed with the disease.

Federal officials estimate that the disease costs about $2 billion in
direct and $4 billion in indirect medical costs each year.

For more information, call (716) 275-7311.



Copyright Union-Tribune Publishing Co.



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