City St George’s, University of London has partnered with Paradigm Biopharmaceuticals to investigate how an experimental osteoarthritis drug may reduce pain linked to bone marrow lesions.

The collaboration will examine injectable pentosan polysulfate sodium (iPPS), a late-stage investigational treatment being developed by Paradigm Biopharmaceuticals for knee osteoarthritis, focusing on its potential effects on bone marrow lesions (BMLs) identified as a key source of joint pain.

Osteoarthritis affects around 10 million people in the UK and more than 600 million globally, with current treatments largely focused on symptom management rather than disease modification.

Research led by Professor Nidhi Sofat at City St George’s has previously identified that osteoarthritis pain is not only associated with cartilage damage but also with BMLs, which are small fluid-filled lesions within the bone that are increasingly recognised as a driver of pain.

The new partnership will analyse the effect of iPPS on BMLs using biopsies collected during total knee replacement surgery. Researchers will combine advanced MRI imaging with gene and protein profiling to assess microscopic changes in bone tissue and better understand disease mechanisms.

iPPS is a semi-synthetic polysaccharide and glycosaminoglycan mimetic derived from beechwood hemicellulose. It is being investigated for its ability to suppress inflammatory pathways by inhibiting the NF-κB protein complex, which plays a central role in regulating inflammation across joint tissues including bone, cartilage and synovium.

Professor Nidhi Sofat, Professor of Rheumatology in the School of Health & Medical Sciences at City St George’s, said: “Bone marrow lesions represent one of the most significant and painful aspects of osteoarthritis, yet we still have much to learn about how best to target them. This collaboration has the potential to deepen our understanding of how pentosan polysulfate works in osteoarthritis.”

She added: “If the drug improves the bone marrow lesions and reduces pain, we hope that it could one day be a new and much-needed treatment option for the millions of people living with osteoarthritis and chronic pain globally.”

Paradigm Biopharmaceuticals, an Australian late-stage clinical development company, is currently evaluating iPPS in a Phase 3 programme for knee osteoarthritis. The company said the collaboration will help generate translational data on the drug’s activity across joint tissues, supporting its ongoing clinical development.

Paul Rennie, founder and executive chair of Paradigm Biopharmaceuticals, said: “This collaboration with City St George’s represents an important step in further understanding the mechanism of action of PPS, particularly in relation to bone marrow lesions, which are increasingly recognised as a key driver of pain in osteoarthritis.”

He added: “By combining advanced imaging with molecular profiling, this study has the potential to generate valuable translational data supporting PPS’ activity across multiple joint tissues.”

Rebecca Paulraj, acting head of business engagement and knowledge exchange at City St George’s, said the partnership demonstrates how academic research can be translated into potential clinical benefit through collaboration with industry partners.

The study will run for one year and has been shortlisted for the SEHTA Healthcare Business Awards.

The collaboration reflects growing interest in bone marrow lesions as a therapeutic target in osteoarthritis, alongside efforts to move beyond symptom control towards disease-modifying approaches.