Novel Therapy for Cartilage Regeneration and Rapid Long-term Pain Relief in Osteoarthritis


Healthcare - Pharmaceuticals & Therapeutics
United Kingdom


Osteoarthritis (OA) is a debilitating joint disease which is characterized by breakdown of the articular cartilage and bone changes. Bone changes include the thickening of the bone supporting the cartilage and excessive bone formation at the margins of the joint (osteophytes). Isolated cartilage defects are found in 61% of all arthroscopies e.g inflammatory arthritis such as rheumatoid arthritis can result in irreversible cartilage loss. If cartilage defects are left untreated, they tend to extend to the healthy cartilage and result in osteoarthritis. Cartilage regeneration in these patients will restore quality of life and revert disability. There are no disease modifying therapies to treat the cause of osteoarthritis. Current treatment consists of symptom management with non-steroidal-inflammatory drugs with patients eventually needing joint replacement. Hence, there is an urgent unmet need for a new therapeutic approach targeting and resolving the aetiology of the disease. Isolated cartilage defects are also very frequent and if left untreated they induce further cartilage loss. The current treatment for isolated cartilage defects includes microfracture and autologous chondrocyte implantation. The outcome of the former is only transient, and the latter involves the manufacturing of each individual patient’s cells, thereby leading to high production costs, small revenues and poor upscalability.


A protein, Agrin, which following a single application, supports robust and long-term cartilage regeneration, has been identified. The striking features include:

  • Its overexpression eliminates pain in a mouse model of osteoarthritis.
  • A small, soluble deletion mutant version of Agrin is efficacious.
  • Agrin is a naturally occurring large, insoluble protein that gets increased after acute injury to cartilage in the human body. Therefore, it will not induce rejection.
  • Through the modulation of two signalling pathways, Agrin induces the recruitment of mesenchymal stem cells within synovial joints, towards the GDF5+ lineage of committed joint morphogenetic cells, which contribute to cartilage repair
  • As opposed to other proteins that can induce cartilage formation (e.g. bone morphogenetic proteins), Agrin supports the formation of stable cartilage which does not turn into bone.


This molecule can be developed into an effective therapy that can cure the primary cause of osteoarthritis compared to current treatments that only ameliorate late-stage symptoms. 


  • Novel therapeutic: regenerates defective cartilage & bone, improves pain management in osteochondral defects.
  • Induces the regeneration & patterning of joint reproducing tissue architecture without inappropriate cartilage formation in ectopic sites.
  • In vivo data show clear efficacy of the therapy for up to 6 months with a single low dose administration in sheep models of critical-sized joint defects.
  • The molecule can be developed into an effective therapy that can cure the primary cause of osteoarthritis, unlike current treatments that only ameliorate late-stage symptoms.
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