Researchers at the University of Birmingham have identified a naturally occurring peptide called PEPITEM that shows promise as a new therapeutic for osteoporosis and other disorders involving bone loss. This peptide, first identified in 2015, has been found to enhance bone mineralization, formation, and strength, and reverse bone loss in animal models of disease. The research, funded by major grants from organizations such as the Medical Research Council and the Lorna and Yuti Chernajovsky Biomedical Research Foundation, aims to develop new targeted medicines to improve health.
Bone is continually formed, reformed, and remodeled throughout life by the interplay between osteoblasts, which form bone, and osteoclasts, which break it down. Disruptions in this process can lead to diseases like osteoporosis and rheumatoid arthritis. While current osteoporosis therapies target osteoclasts to prevent further bone loss, new therapies are needed to stimulate bone repair in age-related musculoskeletal diseases. Researchers like Dr. Helen McGettrick and Dr. Amy Naylor, in collaboration with other institutions, are investigating the potential therapeutic impact of PEPITEM in these conditions.
PEPITEM is a naturally occurring short protein found in the body at low levels. Research has shown that increasing levels of PEPITEM can stimulate bone mineralization in young bones, resulting in increased bone strength and density similar to standard drugs like bisphosphonates and parathyroid hormone (PTH). In animal models of menopause and inflammatory bone disease, PEPITEM has been shown to limit bone loss, improve bone density, and reduce bone damage and erosion. Human bone tissue studies have also demonstrated that PEPITEM can promote the maturation of osteoblasts and enhance their ability to produce and mineralize bone tissues.
Studies have shown that PEPITEM acts directly on osteoblasts to promote bone formation by increasing their activity, rather than their number. The researchers identified the specific NCAM-1 receptor on osteoblasts as the target for PEPITEM, and found that the NCAM-1-b-catenin signaling pathway is responsible for the upregulation of osteoblast activity. PEPITEM also has an effect on osteoclasts and bone resorption, reducing the number of osteoclasts and leading to decreased bone mineral resorption. This effect is mediated by a soluble substance released by osteoblasts activated by PEPITEM.
The findings from these studies suggest that PEPITEM could be a potential treatment for bone-related diseases such as osteoporosis, arthritis, and inflammatory conditions. The researchers have curated the intellectual property associated with PEPITEM, including patent applications covering its activity in inflammation, bone diseases, and obesity-related disorders. A US patent application for the use of PEPITEM in the treatment or prevention of bone diseases was filed in 2019, highlighting the potential for PEPITEM as a novel therapeutic in the field of musculoskeletal research.
Overall, the research on PEPITEM has shown promising results in stimulating bone repair and promoting bone formation in various disease models. Further studies will be needed to investigate the potential clinical applications of PEPITEM in humans, but the findings from these preclinical studies suggest that this naturally occurring peptide could be a valuable addition to the current treatments for conditions involving bone loss.
