Researchers at the University of Birmingham have discovered a naturally occurring peptide (small protein) called PEPITEM that shows potential as a new treatment for osteoporosis and other conditions characterized by bone loss. This peptide has several advantages over current medications. PEPITEM was first identified in 2015 and is known as Peptide Inhibitor of Trans-Endothelial Migration.A new study, which was published in Cell Reports Medicine, has shown that PEPITEM may be used as an innovative early treatment to counteract the effects of age-related musculoskeletal diseases. The research has indicated that PEPITEM can improve bone mineralization, formation, and strength, as well as reverse bone loss in animal models of disease.
Funding for the research was provided by the Medical Research Council and the Lorna and Yuti Chernajovsky Biomedical Research Foundation, which supports groundbreaking research aimed at developing new targeted medications to enhance health. Other supporters included the British Society for Immunology.or Research on Ageing and Versus Arthritis.
Bone undergoes a continuous cycle of formation, reformation, and remodeling throughout a person’s life. About 10% of human bone is replaced each year through the interaction of two cell types — osteoblasts, which create bone, and osteoclasts, which break down bone. Disruptions to this carefully coordinated process contribute to the characteristics of diseases like osteoporosis and rheumatoid arthritis, which involve excessive bone breakdown, or ankylosing spondylitis, which features abnormal bone growth.
The most common treatments for osteoporosis (bisphosphonates) focus on targeting osteoclasts to prevent further bone loss.While there are newly developed ‘anabolic’ agents that can help with new bone formation, their clinical use is limited. For example, teriparatide (parathyroid hormone, or PTH) is only effective for 24 months, and romosozumab (anti-sclerostin antibody) has been linked to cardiovascular events. This highlights the need for new therapies to promote bone repair in age-related musculoskeletal diseases, with osteoporosis being the most common. A team of researchers at the University of Birmingham’s Institute of Inflammation and Ageing, including Dr. Helen McGettrick, Dr. Amy Naylor, Dr. Jonathan Lewis, and Ms. Kathryn Frost, are working on this issue.Researchers from the University of Oxford, including Dr. Chaozong Liu and Dr. James Edwards, embarked on a study to explore the potential therapeutic effects of PEPITEM on various disease conditions. PEPITEM is a natural peptide found in the body at low levels. The study revealed that PEPITEM plays a role in regulating bone remodeling and increasing its presence in the body can promote bone mineralization in non-diseased or pre-osteoporotic “young bones.”The results showed that adding PEPITEM could help prevent bone loss and improve bone density in animal models of menopause and inflammatory bone disease. This is important because it targets the natural repair process that is affected by age and inflammatory disease. The researchers found that the effects of PEPITEM were similar to those of standard drugs like bisphosphonates and PTH, which are currently used to increase bone strength and density. This suggests that PEPITEM could be a potential new therapeutic for osteoporotic bone loss and inflammatory bone disease.
Research using bone tissue from older patients during joint surgery confirmed the findings. The studies revealed that PEPITEM significantly enhanced the maturation of osteoblasts and their ability to produce and mineralize bone tissues in older individuals. In addition to this, cell and tissue culture work demonstrated that PEPITEM directly impacts osteoblasts, promoting bone formation by increasing their activity rather than their quantity. Subsequent studies also identified the NCAM-1 receptor as the specific receptor for PEPITEM on osteoblasts, and strongly suggested the NCAM-1- b-catenin signaling.
Osteoblasts become more active due to the effects of the PEPITEM pathway. It is important to note that this receptor and pathway are different from the previously known PEPITEM receptors found in other parts of the body. Additionally, studies on mice showed that PEPITEM has a significant impact on osteoclasts and bone resorption. The research found that PEPITEM reduces the number of osteoclasts, leading to a decrease in bone mineral resorption. Furthermore, the study revealed that the decrease in osteoclast activity is caused by a substance released by activated osteoblasts in bone tissues. Dr. Helen McGettrick stated, “The activation of osteoblasts by PEPITEM leads to the release of a soluble substance locally in bone tissues which reduces osteoclast activity.”The drugs that are most commonly used, known as bisphosphonates, work by stopping the action of osteoclasts. In contrast, PEPITEM works by shifting the balance in favor of bone formation without affecting the ability of osteoclasts to absorb areas of damaged or weak bone tissue through normal bone remodeling.”
Helen Dunster, the Business Development Manager who has managed the intellectual property associated with PEPITEM for the past 8 years, states: “PEPITEM is the focus of several patent families that cover its effects on inflammation and inflammatory immune-mediated, bone, and obesity-related diseases, as well as smaller PEPITEM pharmacophores. A USThe patent application (US18488234) for PEPITEM’s use in treating or preventing bone disease was filed on 8/10/2019. The article “Therapeutic avenues in bone repair: Harnessing an anabolic osteopeptide, PEPITEM, to boost bone growth” by Jonathan W. Lewis, Kathryn Frost, Georgiana Neag, and others is the journal reference for this application.The study discovered a potential new treatment that can stimulate bone growth and stop bone loss.
