Prions are special proteins believed to be the infectious agents responsible
for transmissible spongiform encephalopathies (TSEs), a group of rare, fatal
disorders that slowly destroy the brain and nervous system. These diseases
include bovine spongiform encephalopathy (BSE, "mad cow disease") in cattle,
scrapie in sheep, chronic wasting disease (CWD) in deer and elk, and CJD in
In each case, the brain accumulates abnormal forms of prion protein. Every
protein in the body must be folded into a specific three-dimensional shape
to be functional. When proteins fold incorrectly, as in prion diseases,
they tend to aggregate and cause disease.
Suzette Priola, Ph.D., and colleagues from NIAID's Rocky Mountain
Laboratories (RML) in Hamilton, MT, studied the effect of cyclic
tetrapyrroles, compounds that include drugs used in cancer therapy, on a TSE
disease in mice. A critical step in the development of TSE diseases occurs
when normal prion protein converts to an altered, disease-causing form.
Previously, a team from RML had reported that cyclic tetrapyrroles block
this conversion in the test tube; now Dr. Priola's team has shown that these
same agents significantly slow TSE disease progression in mice.
Dr. Priola's team injected mice with a high dose of scrapie, which causes
normal prion proteins to convert to the disease-causing form. The
researchers then gave one of three candidate treatment compounds at
different times during the 80-day incubation period. When given at the time
of injection or when mixed with the injection, the compounds extended
survival time dramatically, in some cases by 300 percent. When given later
during disease, they had minimal effect. These results suggest that the
compounds might delay disease if given prior to or early during infection.
They also might be used to treat blood products to inactivate infectious
prions. According to this study, however, they would likely be ineffective
once the disease develops.
"Since diagnosis of CJD in humans can be made only after symptoms appear, we
are trying to identify a compound that works later in the disease," explains
Dr. Priola. "The extremely wide variety of these compounds available for
testing makes our current search for one that can affect disease after the
onset of symptoms much more promising."
Treatment for prion diseases has received renewed interest of late. A new
variant of CJD appeared in England in 1996, coinciding with a BSE epidemic
in that country. Because the new variant closely resembles BSE, health
officials believe the disease jumped from cattle to humans. In the western
United States, CWD in wild deer and elk has become an increasing concern
because of fears it might spread to other species such as cattle and humans.
Other diseases, such as Alzheimer's disease and type 2 diabetes, show a
similar accumulation of misfolded proteins, although they do not involve
prions. Therefore, drugs that block this process might prove effective in
treating these disorders as well.
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conducts and supports research to prevent, diagnose and treat illness such
as HIV disease and other sexually transmitted diseases, tuberculosis,
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