by A groundbreaking study led by researchers from the University of Birmingham and the University of Oxford has revealed that PEPITEM, a naturally-occurring peptide, holds great promise as a novel therapeutic for age-related bone disorders, including osteoporosis. This discovery offers distinct advantages over current treatments, as shown by enhanced bone mineralization, formation, and strength in animal models.
First identified in 2015, PEPITEM, or Peptide Inhibitor of Trans-Endothelial Migration, is a naturally-occurring short protein produced in the body and found circulating in everyone at low levels. The latest research, published in Cell Reports Medicine, demonstrates that PEPITEM plays a crucial role in regulating bone remodeling.
Bone undergoes constant turnover, with approximately 10% being replaced annually. An intricate balance exists between osteoblasts, which form bone, and osteoclasts, which break down bone. Disruptions to this process lead to conditions such as osteoporosis, rheumatoid arthritis, and ankylosing spondylitis, characterized by excessive bone loss or abnormal bone growth. In addition to these bone-related issues, advancements in medical science have also emphasized the importance of soft tissue repair, highlighting the interconnected nature of bone health and overall musculoskeletal integrity
Current osteoporosis treatments, including bisphosphonates, target osteoclasts to prevent further bone loss. Although new anabolic agents can promote bone formation, they have limitations, such as teriparatide’s effectiveness for only 24 months and romosozumab’s association with cardiovascular events.
Given the need for new therapies to stimulate bone repair in age-related musculoskeletal diseases, the research team, led by Dr. Helen McGettrick, Dr. Amy Naylor, Dr. Jonathan Lewis, Kathryn Frost, and Dr. James Edwards, set out to investigate the potential therapeutic impact of PEPITEM in these disease states.
The findings showed that increasing the amount of PEPITEM in the body stimulates bone mineralization in young, healthy bones, resulting in increased bone strength and density similar to current standard of care drugs. Crucially, PEPITEM also targets the natural repair process compromised by age or inflammatory disease.
In animal models of menopause, a common trigger for osteoporotic bone loss, PEPITEM limited bone loss and improved bone density. Similar findings were observed in models of inflammatory bone disease (arthritis), where PEPITEM significantly reduced bone damage and erosion.
Further studies using human bone tissue, harvested from older patients during joint surgery, showed that cells from older individuals responded to PEPITEM, significantly increasing the maturation of osteoblasts and their ability to produce and mineralize bone tissues.
PEPITEM directly affects osteoblasts to promote bone formation, increasing their activity rather than their number. The team identified the NCAM-1 receptor as the specific receptor for PEPITEM in osteoblasts and strongly suggested the NCAM-1-β-catenin signaling
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