(photo credit: Courtesy)
The discovery by a Hebrew University of Jerusalem team of a connection between bone density and fatty acids has led them to begin developing a drug they hope will more effectively treat – and even prevent – the debilitating bone-thinning disease of osteoporosis.
Their paper has just been published in the Proceedings of the National Academy of Sciences, the official journal of the American academy.
The research team is headed by Prof. Itai Bab of the university’s bone laboratory and Prof. Raphael Mechoulam of the Institute of Drug Research, who is a world-renowned expert on the active ingredients in cannabis. Other members include post-doctoral fellow Reem Smoum and doctoral students Gary Millman, Orr Ofek, Alon Bajayo, Joseph Tam, Vardit Kram and associates from the US.
Osteoporosis, the most widespread degenerative disease in the Western world, affects mostly women after menopause but also a minority of men. It causes the bones to be fragile from the loss of bone mass, leading to frequent bone fractures, disability and even death. The loss of bone mass in osteoporosis is caused by internal destruction of the bone tissue. With age, the quantity of bone tissue that is lost is greater than that which is created, which leads to the decrease in bone density.
Working on lab mice, the team discovered a group of substances – fatty acids and amino acids called “acyl amides” – in the body that play a key role in controlling bone density. They then analyzed their precise chemical composition, created synthetic versions of them and examined their effect on bone cell cultures.
In their lab experiments, they discovered that one of the compounds in the group of synthetic materials, oleoyl serine, increased bone density in both healthy mice and those with osteoporosis. They also found that the osteoporotic mice lacked oleoyl serine in their bones.
These findings, say the researchers, can serve as the basis for new drugs that may both prevent bone loss and boost bone formation and in this way reverse loss of bone tissue in osteoporosis patients.
Yissum, HU’s technology transfer company, has submitted a patent application based on their work and is seeking a commercial partner for further development.
Mechoulam felt certain that their work showing bone mass accumulation
would lead soon to the development of an effective osteoporosis drug.
Existing medications, such as biphosphonates, help either prevent
further bone loss or encourage bone formation, but none of them is able
to accomplish both functions together as this new formula can do, said
Bab. In addition, some of the other drugs have unpleasant side effects.
The researchers noted that research in this field until now has been
based primarily on proteins and genetics. Now, the Jerusalem researchers
say, they have launched a new approach called “skeletal lipidomics”
based on the examination of substances in the skeleton containing fatty
acids and amino acids. This has great significance in understanding the
regulation of metabolism in bone and in other body tissues, they said.
The research has been supported by the US-Israel Binational Science
Foundation and a grant from the US National Institutes of Health.