30 Aug 2017 --- An herb used in Traditional Chinese medicine (TCM) might be crucial to a new osteoporosis therapy that could prevent bone loss without causing side effects, according to a new study by researchers at the University of British Columbia (UBC).
Using a compound derived from red sage, known as Danshen in Chinese, UBC researchers have found a way to selectively block an enzyme called Cathepsin K (CatK), which plays a major role in the breakdown of collagen in bones during osteoporosis. The researchers’ findings have been published in the Journal of Bone and Mineral Research.
Osteoporosis is a global health problem that will affect one out of three women and one out of five men worldwide, and there is a multibillion-dollar pharmaceutical industry dedicated to finding treatments to stop its progression, according to UBC’s press release.
“The development of osteoporosis drugs by pharmaceutical companies has focused heavily on blocking CatK in recent years,” says Dieter Brömme, a professor in the faculty of dentistry and a Canada Research Chair in Proteases and Disease of previous efforts. “All clinical trials to date have failed due to side effects ranging from stroke, skin fibrosis and cardiovascular issues. We've found a way to block CatK only in bone tissue that we think will prevent these other negative effects.”
Compound holds key The researchers tested a compound derived from red sage in human and mouse bone cells and a mouse model. They found that it prevented bone loss and increased the bone mineral density of the mice treated with the compound by 35 percent when compared with the control group.
The study builds on previous research by Brömme and his team that looked at the effectiveness of red sage, used to treat bone ailments in traditional Chinese medicine, in stopping the activity of CatK in limited ways.
Enzyme blockers work like keys in locks, notes UBC’s press release. Most drugs in development have been so called active site-directed inhibitors, which act like master keys and lock the entire enzyme, blocking both its disease-relevant functions such as collagen degradation and its other normal functions.
“CatK is a multifunctional enzyme with important roles in other parts of the body and we think completely blocking it is what causes unexpected side effects in other drugs,” explains Preety Panwar, a research associate in the Brömme lab. “Our compound only locks the collagen-degrading CatK activity, preventing the unregulated breakdown of collagen in bones without any other negative impacts.”
The treatment could also potentially be used to treat a variety of other bone and cartilage diseases such as arthritis and certain bone cancers.
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