Vaccine Inhibits Bone Destruction in Animal Models of Osteoporosis, RA

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Vaccine Inhibits Bone Destruction in Animal Models of Osteoporosis, RA

WESTPORT, CT (Reuters Health) Oct 15 - An experimental vaccine that targets the

receptor activator of

nuclear factor kappa-B ligand (RANKL) has shown promise in limiting pathological

bone loss in mouse models

of osteoporosis and rheumatoid arthritis.

Dr. Marc Hertz of Pharmexa A/S, Horsholm, Denmark, described the early results

with RANKL AutoVax on

Friday in Phoenix, Arizona, during the 23rd Annual Meeting of The American

Society for Bone and Mineral

Research. The study was conducted by Dr. Takuo Juji of the University of Tokyo

and colleagues.

In a telephone interview with Reuters Health over the weekend, Dr. Hertz noted

that RANKL, a member of the

tumor necrosis factor family of cytokines, is known to play a key role in

osteoclast differentiation and activation

and in normal bone development. Evidence is mounting, he said, that RANKL also

plays important roles in

conditions that involve pathological bone destruction, such as osteoporosis and

rheumatoid arthritis.

RANKL AutoVax, which contains a modified version of RANKL, generates a rapid and

sustained antibody

response that can neutralize RANKL in vivo, Dr. Hertz told Reuters Health.

Female BALB/c mice immunized with the vaccine four times at 2-week intervals

were resistant to bone loss in

response to ovariectomy. Importantly, the scientist said, mice treated with

RANKL AutoVax showed a

significant reduction in the number of osteoclasts per bone surface compared

with control mice.

In SKG mice, a model of rheumatoid arthritis, RANKL AutoVax immunization reduced

osteoclasts by 62% and

almost completely prevented bone destruction.

" We're now developing humanized versions of this vaccine, " Dr. Hertz told

Reuters Health. " They are going into

preclinical development and we hope to enter phase I trials in 2003. "