Johns Hopkins Gazette: March 6, 1995

Prednisone Could Be Part of Alzheimer's Treatment

By Gary Payinda

     Researchers at Johns Hopkins and 11 other national cites are
beginning a 15-month study to determine whether the body's
natural response to trauma--inflammation--is somehow connected to
the onset and progression of Alzheimer's disease.

     The study is based on research begun in Sweden, which tested
the effects of aspirin, a mild anti-inflammatory drug, on
arthritis. In the course of the investigation, scientists
discovered that aspirin not only slowed the progression of
arthritis, but also had an effect on Alzheimer's disease. The
study remained inconclusive, however, because of the limited
number of Alzheimer's patients involved.

     The current national clinical trials will refine the work
done in Sweden. Prednisone, the strongest anti-inflammatory drug
available, will be used on a large cohort of test subjects (8 to
12 at Hopkins, 150 nationally) and for a longer trial period. The
trials also will focus on the behavioral neuropsychiatric
symptoms of Alzheimer's disease, like forgetfulness and dementia.

     "Previous treatments have largely focused on replacing what
the disease destroyed, like neurotransmitters," said Constantine
Lyketsos, professor of psychiatry and behavioral sciences and
director of the Hopkins portion of the National Alzheimer's
Disease Collaborative Study. "This experiment represents an
attempt to keep the brain healthy and to prevent the damage
before it begins."

     Immediately after an injury, immune system proteins come out
of the lymph fluid and blood and congregate around the wound.
These proteins, called acute phase reactants, initiate the
cascade of events known as inflammation. APRs call immune cells
to the site of the injury where they remove dead and damaged
tissue and clean the area, priming the tissues for healing.

     By the time the cleanup is under way, APRs have usually
stopped their migration to the site of the wound and the
inflammation recedes.

     In some cases, however, the inflammation does not subside.
When this occurs on the skin, for example, we get a rash. When it
occurs in the joints, we get arthritis. Researchers believe that
for some reason, this occurs in the brain, and Alzheimer's
disease may either result from or become exacerbated by the
body's wayward defense system.

     Treatment with prednisone will suppress inflammation,
preventing buildup of APRs. Scientists believe that this
accumulation of APRs in the brain chokes neurons, interfering
with their ability to successfully conduct the currents necessary
for normal brain activity. As these neurons eventually die, the
disease progresses irreversibly. Researchers hope that prednisone
will prevent the initial influx of APRs and keep the neurons
alive longer.

     Dr. Lyketsos, while enthusiastic about the new direction of
Alzheimer's research, is cautious about expected findings,
because, he said, there are many aspects to Alzheimer's disease
besides the immune system, such as the environment and the
patient's genetic makeup.

     "Even if the prednisone is effective and can reduce
inflammation in the brain, anti-inflammatory therapy would
probably constitute only one aspect of a complete treatment for
[a patient with] Alzheimer's disease," he said.

     Dr. Lyketsos hopes the drug treatment will be able to retard
the spread of the disease in its earliest stages, which in itself
would be a therapeutic breakthrough.

     "Though we might not achieve an outright reversal of the
disease, you've got to keep in mind that the majority of these
patients are elderly," he said. "The ability to significantly
slow a disease like Alzheimer's, one with a time course of up to
15 years, could--for many--prove to be tantamount to a cure."

     Alzheimer's disease affects about 5 million people in the
United States, about one in 50 Americans.

     Dr. Lyketsos is seeking additional volunteers for the study.
For information, contact Elizabeth Galik, of the Neuropsychiatry
and Memory Group at Copper Ridge in Sykesville, Md., at (410)
795-8808, ext. 108.

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