Vaccine (RANKL) Inhibits Bone Destruction in Animal Models of Osteoporosis, RA

October 22, 2001

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. "

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