A natural protein in the body can be tailored to function as a multitargeting drug to treat osteoporosis, a disease in which the bones become brittle and fragile, according to a new study by Ben-Gurion University of the Negev (BGU) researchers.

The researchers reveal in the scientific journal, PLOS Biology, that by targeting two cell receptors simultaneously, the engineered proteins may provide relief for osteoporosis patients with fewer adverse side effects than current treatments.

According to the International Osteoperosis Foundation, 44 million people in the United States have either osteoporosis or low bone mass, which represents 55% of people aged 50 and older.

“Osteoporosis is caused by a disturbance of the normal balance between the production of new bone tissue and the breakdown of old tissue by bone-removing cells, known as osteoclasts,” says Dr. Noam Levaot of the BGU Department of Physiology and Cell Biology.

Current drugs for osteoporosis work by completely shutting off this breakdown, known as bone absorption, for an uncontrolled duration. This increases the risk for adverse side effects, such as low blood calcium, atypical fractures, and destruction of the jaw bone.

“These problems limit the use of currently available drugs and lead to poor patient compliance,” Dr. Levaot says. “Despite the progress in treatment of patients with osteoporosis, there remains a significant demand for safer and more specific osteoporosis drugs with a prolonged biological effect.”

This new drug is based on a natural human protein that has been modified to inhibit the bone destruction activity of osteoclasts by simultaneously targeting two receptors (communication sites) present on these cells. They showed that in an animal model for osteoporosis the drug is very specific to osteoclasts and can effectively prevent bone absorption.

“We believe that such modified proteins could provide the next generation of therapeutics with targeted activities and fewer adverse side effects. We are also confident that such modified protein compounds could also work on other bone diseases and certain types of cancer, particularly metastatic bone cancer,” says co-researcher Dr. Niv Papo of the BGU Department of Biotechnology Engineering and the National Institute for Biotechnology in the Negev. PhD student Yuval Zur also participated in the study.