Gene May Be Target for Osteoporosis Treatment
It appears to regulate bone mass in mice
THURSDAY, Jan. 8, 2004 (HealthDayNews) -- A gene that plays a role in heart disease now appears to be a potential target for treatment of osteoporosis, the bone-thinning condition that affects many older women.
The gene, dubbed Alox15, is part of a pathway that determines whether cells in marrow become either bone or fat, explains Dr. Robert F. Klein, lead author of a paper describing the finding in the Jan. 9 issue of Science.
The research, which involves mice, already has at least one pharmaceutical company working on drugs aimed at altering activity of the gene to combat osteoporosis.
Dr. Gary Peltz is director of genetics at Roche Palo Alto, a division of Hoffmann-La Roche Inc., and is also an author of the Science paper. He calls the research a good example of how basic science can point the way to the development of new disease treatments.
"We developed the technology to analyze this mouse model of human disease," Peltz says. "Then we try to utilize that model for therapeutic purposes."
The osteoporosis research started with a genetic analysis of inbred mice, comparing their physical characteristics with their genetic makeup, Klein says. That analysis showed bone density in the mice was related to the activity of the Alox15 gene.
"Animals that had overexpression of the gene had the lowest bone density," Klein says. "Knockout mice, which do not have the gene, have very high bone mass."
In mice, Alox15 lies on chromosome 11. The same gene is found on chromosome 17 in humans, Klein says.
At Roche Palo Alto, Peltz and his colleagues are using a two-pronged approach to develop possible osteoporosis treatments. They are reviewing a large library of chemicals to see whether any of them affect activity of the gene. They're also trying to design molecules that might help build bone mass by inhibiting the gene's activity.
Klein, who is an associate professor of medicine at the Oregon Health & Science University and the Veterans Affairs Medical Center in Portland, is pressing ahead with research aimed at "understanding how this pathway evolved in normal mice."
"This is teaching us a lot more about the complexity of bone physiology," he says. "It is pretty much basic science."
But that science already is being applied to possible treatments for osteoporosis, and not only by the Roche group, Klein says. "Others are studying human populations, to see whether this genetic pathway in humans is responsible for osteoporosis," he says.
An estimated 10 million Americans -- 80 percent of them women -- have osteoporosis, and 18 million more have low bone mass, placing them at risk for the disease, U.S. health officials report.