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Dual-Specific R-Protein as an Anti-Resorptive Treatment
for Bone-Related Disorders



Osteoporosis (OP) is a common chronic skeletal disorder in aging individuals. In-spite of the progress made in this market, there is still a great demand for safer and more specific drugs for extended administration.  Excessive bone resorption by osteoclasts is central to the pathogenesis of OP and other bone-related diseases. Thus, inhibition of osteoclast activity is a desired outcome in the treatment of bone and bone-related disorders. However, complete irreversible shutdown of resorption by current drugs and uncontrolled duration of activity increase the risk for hypocalcemia, atypical fractures and osteonecrosis of the jaw limiting their utilization and decreasing patient’s compliance to their administration.

The combined expression of M-CSF receptor c-FMS and αvβ3 integrin is unique to osteoclasts. Moreover, signaling through these receptors is essential to organize the osteoclast cytoskeleton elements and for its resorption machinery. Studies in animal models demonstrated that interfering with signaling through these two receptors inhibits resorption but still enables bone formation to go on. 


The Technology

A new generation of bispecific proteins based on the natural ligand M-CSF as a scaffold to engineer novel c-fms/avb3 integrin antagonists i.e. dual specific antagonists (DSA), with the improved properties required for their application as anti-resorptive drugs in bone diseases and osteoporosis therapy.  Current results demonstrated effective inhibition of osteoclast differentiation with the identified DSAs compounds compared to a variant that targets c-fms alone. In an additional in-vivo proof of concept experiment, the compounds extensively downgrade bone resorption in an ovariectomized female mouse osteoporosis model.




  • A fresh approach with a novel mechanism of action for bone-related diseases in which controlled inhibition of resorption is required.
  • The compounds preferably target cells expressing both receptors increasing its safety and efficacy.
  • The compounds are based on a small natural protein enabling flexible control of their concentration and retention, thereby providing control on the level and duration of action.
  • Targeting resorption through the αvβ3 integrin axis should permit bone formation to continue decreasing side effects and enabling the utilization of the drug in treatment, which combine anti- resorptive together with bone promoting drugs (Anabolic drugs).


Patent Status


PCT patent application No. PCT/IL2017/050921 filed August 18, 2017
National phase entry in: Australia, China, Canada, Israel, Europe, Hong Kong and USA     


Principal Investigators


Prof. Niv Papo, NIBN and the Department of Biotechnology Engineering and Dr. Noam Levaot, Department of Physiology and Cell Biology, Ben-Gurion University of the Negev, Israel