Boston, Dec. 15, 2003---Scientists at The Forsyth Institute have
discovered that a compound found in scorpion venom significantly inhibits
bone loss found in a model of advanced periodontal disease. The compound may
also one day be useful in allaying the bone-destroying effects of
inflammatory diseases such as osteoarthritis and rheumatoid arthritis, the
research suggests.
The compound, kaliotoxin, was effective in preclinical studies.
"We are very excited because this is the first demonstration that this
type of compound (called a potassium channel blocker) may be useful in
treating periodontal disease," said Martin Taubman, DDS, PhD, chair of the
Forsyth Department of Immunology, in whose laboratory the research was
carried out. "We hope that our findings will lead to success in alleviating
the bone-ravaging effects of many other diseases."
At least one-fourth of US residents over age 30 have periodontal disease
involving loss of bone or teeth, according to the National Institute for
Dental and Cranial Research. Some 21 million individuals in the US are
affected by osteoarthritis and nearly 2.1 million have rheumatoid arthritis,
according to a 1998 study provided by the Arthritis Foundation.
The Forsyth scientists report in the January 2004 Journal of Bone and
Mineral Research that they induced the bone loss component of
periodontal disease in rats and injected one group with kaliotoxin. After
ten days, animals injected with kaliotoxin exhibited 84 per cent less
alveolar (jaw) bone loss than did those that did not receive injections.
According to Paloma Valverde, Ph.D., the principal investigator,
kaliotoxin modulates inflammatory bone resorption by blocking the protein
Kv1.3, a potassium channel known to be involved in inflammation. "Kaliotoxin
decreases the expression of RANKL, a protein expressed on the surface of
memory/activated T cells, which are present at high levels in periodontal
disease," she said. RANKL plays a key role in inducing bone cells called "osteoclasts"
to destroy bone. Thus, kaliotoxin or other potassium channel blockers that
target Kv1.3 may reduce bone resorption.
"This is the first known study to show that a potassium channel blocker
can decrease alveolar bone loss," Valverde said. "Furthermore, we observed
no toxic effects. Therefore we now have a novel and apparently safe strategy
to ameliorate bone destruction associated with periodontal disease. We
expect that kaliotoxin and other Kv1.3 blockers can also be used to prevent
bone destruction in other inflammatory bone resorptive disorders such as
osteo- and rheumatoid -arthritis."
Other components of scorpion venom are being studied elsewhere for
possible uses in treating autoimmune diseases such as multiple sclerosis and
lupus; stroke and heart disease; and certain cancers.
The study, "Kaliotoxin Decreases Alveolar Bone Resorption," was conducted
at The Forsyth Institute by Valverde, Toshihisa Kawai, DDS, PhD, and Taubman.
Valverde conducted her research as a Staff Associate at Forsyth and
Instructor in Oral Biology at the Harvard Dental School. She is now a
Scientist II at the USDA Human Nutrition Research Center on Aging at Tufts
University. Dr. Kawai is an Assistant Member of the Staff at Forsyth and an
Instructor in the Department of Oral and Developmental Biology at the
Harvard School of Dental Medicine.
The study was funded by the J.W. Hein Fellowship at The Forsyth Institute
