Medical University of South Carolina www.musc.edu News release 11-1-00 is at: http://www.musc.edu/pr/msdrug.htm ..............The press release: Click here

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MUSC researchers offer hope against MS

Thursday, November 2, 2000
By LYNNE LANGLEY
Of The Post and Courier staff

A drug commonly prescribed to lower cholesterol may help relieve symptoms and
slow progression of multiple sclerosis, Charleston doctors announced Wednesday.
Medical University of South Carolina doctors will direct a national trial,
beginning next month, in which MS patients take simvastatin (brand name Zocor)
for six months to determine whether the drug is safe and effective.
If it is, the drug that more than 20 million people have taken worldwide may
leap onto the federal Food and Drug Administration's fast track for approval
to treat MS.

The medicine worked dramatically on rats in the MUSC laboratory of Dr.
Inderjit Singh.

Rats with MS had increasing difficulty moving and became partially paralyzed.
Rats given the drug, however, didn't just get up and walk. They romped around
and ran in their exercise wheels.

All the treated rats completely recovered while those with MS that did not get
the drug died, said Dr. Lyndon Key, the MUSC pediatrics professor who is
principal investigator for the national trial.

"With lovastatin (a related drug) and simvastatin, this disease can be
reversed," said Key. The drugs delayed symptoms, reduced their severity and
led to complete recovery of the animals, he said.
"This is a very important new study," said MUSC President Dr. Ray Greenberg.
"It's a wonderful example of taking basic research from the lab and applying
it ... to benefit patients."

The medicine works by fighting inflammation, which causes damage in the brains
of MS patients, Key said. And, it has implications for treating other illnesses
caused by inflammation, such as stroke, Alzheimer's and spinal chord injury,
Key said.

In the MS trial that starts next month, patients will have a series of MRIs to
show how lesions in their brains - and thus their MS - respond to the medicine,
Key said.

"Dr. Singh's research implies significant effect," said Dr. Timothy Vollmer,
who will lead a branch of the drug trial at Yale University.
MS affects 350,000 people in the U.S. and 2.5 million worldwide, he said,
adding that it costs the U.S. economy $10 billion a year.
MS patients may have difficulty walking, moving or thinking and may suffer
vision problems or incontinence. The symptoms eventually progress to blindness,
paralysis and death.

The four drugs approved for use thus far, all injections that cause side
effects, only affect the course of MS moderately, Vollmer said. Patients
report few side effects from the cholesterol-lowering drug.
"We are not sure that a patient severely crippled will be able to get up and
walk, but young, newly diagnosed patients will have a better future," said Dr.
Charles Darby, chairman of the MUSC pediatrics department.
Singh, a professor of pediatrics and cell biology, began what colleagues
describe as ground-breaking research on the uncommon pediatric illness,
Lorenzo's disease.

Singh's work on Lorenzo's disease, which causes the brain to degenerate, led
to research on MS, which also results in destruction of nervous system tissue.
Patients will begin enrolling in the study next month at MUSC, Yale and the
University of Colorado, 10 patients at each health center.
The trial might take a year, Key said.
Results, collected and analyzed at MUSC, could then go to the FDA, which will
weigh whether the drug is safe and works on MS. MUSC might immediately
petition FDA to approve the drug for MS, Key said.

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http://www.musc.edu/pr/msdrug.htm

Medical University of South Caroline
Office of Public Relations
171 Ashley Ave., P.O. Box 250401
Charleston, SC 29425
voice: 843-792-3621
fax: 843-792-6743

Contact: Ellen Bank 843.792.2626

Nov. 1, 2000

EMBARGO: FOR RELEASE WEDNESDAY, NOV. 1, 2000, 11 A.M. EST

Clinical Trial on Promising Drug for Multiple Sclerosis to Begin

The Medical University of South Carolina (MUSC) will direct a multi-center
clinical trial on a drug promising to relieve symptoms and halt the progression
of multiple sclerosis (MS).

Medical University basic researchers have already shown the efficacy of a class
of drugs known as "statins" in reducing brain damaging inflammation in cell
culture and experimental animals.

The clinical trial is designed to determine if one of these medications,
simvastatin, is an effective treatment for MS. "This is an extremely promising
drug," said Lyndon Key, M.D., principal investigator for the trial and professor
of pediatrics at MUSC. Simvastatin is a common cholesterol-lowering drug. It is
registered in 117 countries, and more than 20 million people have been treated
with the drug. It offers advantages over medications currently taken for
multiple sclerosis which are administered by injection and may cause side
effects in a significant number of patients. Simvastatin is administered
orally and has minimal side effects. In addition, it is much less expensive.

MS patients will be enrolled in the study at the Medical University, Yale
University and the University of Colorado's Denver Health Sciences Center.
Thirty patients (10 at each site) with active brain lesions will be enrolled
in the treatment phase of the trial. They will take the drug daily for a
six-month period, while a series of MRI scans will allow the investigators to
observe a reduction or changes in the lesions. It is an open labeled clinical
trial with all participants given active medication.

Key is conducting the trial in conjunction with MUSC's Clinical Innovation
Group, which designs the study, centrally manages the research at each
institution, and collects and evaluates data. Each site has a designated
clinical principal investigator for the study site. William Tyor, M.D.,
director of the MUSC Multiple Sclerosis Clinic, will be clinical principal
investigator for the MUSC site; Timothy Vollmer, M.D., director of the Yale
University Multiple Sclerosis Research Center, for the Yale University
Multiple Sclerosis Research Center, for the Yale University site; and John
Corboy, vice chairman of neurology at the University of Colorado Health
Sciences Center, for that site.

"This project is an excellent example of an academic medical center at its
best," said Medical University President Ray Greenberg, M.D., Ph.D. "Important
research at the basic science level has been carried out in the laboratories
of our institution. This research has gone through rigorous peer review, and
the results were published in scientific journals. Based on those results, our
own faculty members with expertise in clinical research have developed a
national clinical trial to test the laboratory findings on patients who would
likely benefit.

Multiple sclerosis usually begins in early adulthood with symptoms varying in
severity and duration. Remissions are common in early stages of the disease.
Blurred or double vision, inflammation of the optic nerve, muscle weakness and
dizziness are some of the initial symptoms. In later stages, patients may
endure paralysis, blindness and incontinence. Some 350,000 people in the
United States have multiple sclerosis.

In multiple sclerosis, inflammatory cells enter the brain and start activating
brain cells to produce a variety of toxins that damage myelin sheaths that
surrounds nerves. This may prevent the transmission of messages between the
brain and the rest of the body. When the transmission is blocked, the messages
may be slowed or blocked, causing diminished or lost function.

"We don't know what causes the initial insult in multiple sclerosis, but we do
know that the damage is caused by inflammation," Key said. "The process can be
compared to a computer key and the resulting letter that comes up on your
monitor. You can press the computer key, but if the internal working of your
computer is disrupted, the letter would not appear on your screen." Patients
with MS experience an insult to the body, and their brain cells becomes
damaged due to inflammation. There are intermediary biochemical events required
to cause the inflammatory response. In earlier laboratory work led by Inderjit
Singh, Ph.D., statin drugs were found effective in interrupting these
intermediary biochemical events and thereby blocking the activation in the
inflammatory cells.

Singh is a professor of pediatrics and cell biology & anatomy at MUSC. "Dr.
Singh's work has groundbreaking implications, not just for multiple sclerosis,
but for a variety of other conditions such as stroke, trauma and Alzheimer's
disease, which are also triggered by an inflammatory response," Key said. "His
work in treating multiple sclerosis in a laboratory animal model with
simvastatin showed remarkable results and was the impetus for this clinical
trial. His earlier work with another statin drug in both culture cells and
another disease model was published in major scientific journals and was an
important stepping stone for the current trial." The Medical University has
received an unrestricted medical school grant from Merck & Co. for this
research. Criteria for inclusion in the study include clinically definite MS,
18 - 55 years of age, more than one documented relapse within two years entry,
contraception in females with reproductive potential, EDSS score 0 - 5.5.
Patients interested in enrolling in the trials should contact Ingrid Ingram,
project manager with The Clinical Innovation Groups, at 843-876-1264.

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Zocor may prevent Alzheimer's also...

Actual link: http://www.cnn.com/2001/HEALTH/conditions/05/01/alzheimers.cholesterol/index.html

Text from above:

Cholesterol drug may prevent Alzheimer's


May 1, 2001
Web posted at: 11:28 AM EDT (1528 GMT)

From Rhonda Rowland
CNN Medical Unit

ATLANTA, Georgia (CNN) -- It's already known to dramatically reduce heart attacks and strokes. Now there's evidence that a commonly used cholesterol drug may also prevent Alzheimer's disease.

About 4 million Americans now suffer from Alzheimer's disease, and that number is expected to quadruple in coming years as the population ages. But scientists believe that statins -- better known by the brand names Lipitor, Zocor and Pravachol -- could help delay memory loss.

"What we found was that patients taking statins have a 60 to 70 percent reduction in the risk of Alzheimer's disease," said Dr. Benjamin Wolozin of Loyola University Medical Center in Illinois.

Scientists may have thought the surprising results a fluke, but a second study by a different research team came to the same conclusion.

RESOURCE
Learn more about
Alzheimer's Disease


"This is something that could be an important link, important future treatment for Alzheimer's," Wolozin said.

More studies under way
Researchers say the new findings make sense, since evidence has been accumulating from animal studies that cholesterol contributes to the build-up of amyloid plaques in the brain, a characteristic of Alzheimer's disease.

Although statins are considered safe and have few side effects, researchers say it would be premature to begin using them to prevent dementia or treat Alzheimer's.

The first study in the United States is under way to see if Lipitor is effective in treating the disease.

"We're attempting to slow the progression of the disease, based on the premise that there's this intimate link between cholesterol and the Alzheimer's toxin, beta amyloid," said scientist Larry Sparks of the Sun Health Research Institute in Arizona.

European researchers are studying the effects of Pravachol in almost 6,000 elderly people at risk for both cardiovascular disease and Alzheimer's.

"The aim in this study is to show that the use of Pravastatin to reduce their cholesterol levels will significantly reduce heart attacks, significantly reduce strokes and, most importantly, have an effect on the progression of cognitive decline," said Dr. Ian Ford of the University of Glasgow in Scotland.

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