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Nov/Dec 2000
Vol. 3, No. 9, p. 14.

news in brief

High-affinity bonus

Opening ArtOsteoporosis could be much improved by bone growth factors (BGFs), which are known to stimulate bone formation in vivo. But once they are in the bloodstream, they often do not localize to the sites where they are needed, and instead disseminate to extraskeletal sites.

That tendency has researchers casting about for methods to target BGFs specifically to sites of bone formation, and new research suggests that the aminobisphosphonates (aminoBPs) may be the answer. These molecules travel directly to sites of bone resorption and inhibit the reuptake of bone, thus slowing osteoporosis but not reversing it.

“When we started this work, the basic idea was to induce bone formation from scratch,” says Hasan Uludag, an assistant professor at the University of Alberta in Edmonton, Canada. AminoBPs have a high affinity for bones with high mineral content, and they were a good candidate to conjugate to BGFs and perhaps guide the factors to sites where they could reverse osteoporosis by encouraging new bone formation.

But the aminoBPs proved difficult to work with. “What we discovered was that the aminoBPs were not very [chemically] reactive—there was a particular chemistry that we were using, and it just wouldn’t work,” says Uludag. Within months of changing their approach, they had positive results.

Earlier, the team successfully conjugated aminoBPs to albumin as a model for BGFs. More recently, they compared the levels of albumin, alone or conjugated to aminoBPs, in rats and in the presence of high concentrations of competing proteins (Biotech. Prog. 2000, ASAP Article). In bone sites, they found 8–12 times more conjugated proteins than unconjugated proteins.

The team is now working to confirm the results with BGFs themselves. “Our main philosophy is that if we can get the protein to the right site, we will be able to stimulate bone formation,” says Uludag. “We are not interested in pharmacological activity [of aminoBPs]—all we care about is that they can get to bone.”


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