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New therapeutic avenues in bone repair

Peptide Inhibitor of Trans-Endothelial Migration (PEPITEM), a naturally occurring peptide (small protein) may hold promise as a new therapeutic for osteoporosis and other disorders that feature bone repair and loss, with distinct advantages over existing drugs.

The latest research shows for the first time that PEPITEM could be used as a novel and early clinical intervention to reverse the impact of age-related musculoskeletal diseases, with data demonstrating that it enhances bone mineralisation, formation and strength, and reverses bone loss in animal models of disease.

The most commonly used osteoporosis therapies (bisphosphonates) target osteoclasts to prevent further bone loss. Although there are new ‘anabolic’ agents that can promote new bone formation, there is an opportunity to develop new therapies to stimulate bone repair in age-related musculoskeletal diseases.

Researchers led by Dr Helen McGettrick and Dr Amy Naylor, including Dr Jonathan Lewis and Ms Kathryn Frost, from the Institute of Inflammation and Ageing at the University of Birmingham and Dr James Edwards from Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences at the University of Oxford set out to investigate the potential therapeutic impact of PEPITEM in these disease states.

The research findings demonstrated that PEPITEM regulates bone remodelling and that increasing the amount present in the body stimulates bone mineralisation in ‘young bones’ that are not in a diseased or pre-osteoporotic state, and that this translates to an increase in bone strength and density similar to current standard of care drugs (bisphosphonates and PTH).

However, the key test for a potential new therapeutic is its ability to target the natural repair process that is compromised by age, or inflammatory disease. Here the researchers showed that giving additional PEPITEM limits bone loss and improves bone density in animal models of the menopause, which is a common trigger for osteoporotic bone loss in humans. Their studies also showed similar findings in models of inflammatory bone disease (arthritis), where PEPITEM significantly reduced bone damage and erosion.

These findings were underscored by studies using human bone tissue, harvested from older patients during joint surgery which showed cells from older individuals respond to PEPITEM, significantly increasing the maturation of osteoblasts, and their ability to produce and mineralise bone tissues.

Their cell and tissue culture work showed PEPITEM has a direct effect on osteoblasts to promote bone formation, by increasing the activity of osteoblasts rather than their number. The researchers also investigated PEPITEM’s effect on osteoclasts and bone resorption.

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Joanna Harvey
Joanna Harvey
Marketing and Communication Executive | Uniphar Commercial

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