Acceleron Pharma, Inc., a biopharmaceutical company developing protein therapeutics for cancer and orphan diseases, presented preclinical data highlighting the significant anabolic bone effects in normal and osteopenic mice of RAP-661. Treatment with the investigational compound showed increased bone mineral density, increased osteoblast activity and decreased osteoclast activity. Aaron Mulivor, Ph.D. from Acceleron presented these data at the 3rd Joint Meeting of the European Calcified Tissue Society & the International Bone and Mineral Society in Athens, Greece, 7-11 May 2011.
The bone morphogenetic protein receptor type 1A (BMPR1A) is a high-affinity receptor for members of the BMP family, which contribute to the development and remodeling of bone. ACE-661 is a soluble fusion protein consisting of the extracellular domain of human BMPR1A and the Fc portion of human IgG1. RAP-661 is a murine version of ACE-661. In this study, mice underwent an ovariectomy (OVX) and were aged to establish bone loss. A control group underwent sham surgery and did not develop bone loss. The OVX and sham surgery mice were each separated into treatment groups to receive one of the following: twice weekly injections of RAP-661, the bone anabolic agent parathyroid hormone (PTH), the antiresorptive agent zoledronate, or placebo.
Summary of results:
- After six weeks of treatment, RAP-661 significantly increased trabecular bone (tibia) volume and cortical bone (femur) thickness compared to placebo in both OVX and sham-treated mice.
- Whole-body bone mineral density (BMD) as measured by DEXA after six weeks' treatment in OVX mice revealed that RAP-661 increased BMD from baseline by 14%, compared with increases of 14% for PTH, 7% for zoledronate, and 2% for placebo. In sham-treated mice with no bone loss, RAP-661 increased whole-body BMD by 12%, compared with increases of 9% for PTH, 8% for zoledronate and 1% for placebo.
- Bone mechanical strength was significantly increased in RAP-661 treated OVX mice.
- Histomorphometry and serum biomarker analysis showed an increase in osteoblast activity and a reduction in osteoclast activity, suggesting that RAP-661 has both anabolic and anti-resorptive effects.
"Over the past two decades, scientists and clinicians have recognized the important roles that BMPs play in the development and remodeling of bone," said Ravindra Kumar, PhD, Vice President of Cell Biology at Acceleron Pharma. "The rapid and significant increases in bone mass, volume and strength we observed with systemic administration of RAP-661 are remarkable. These results expand our understanding of bone biology and support the therapeutic potential for ACE-661 in patients with bone loss."