Therapeutic Treating or Preventing Enthesopathy

 
Unmet Need
Over half of sports injuries involve tendons and entheses (the sites of attachment between ligament and bone). Enthesopathy, a disorder involving the attachment of tendon or ligament, represents one-fourth of tendon diseases and is a difficult disorder to treat. Tendon disorders, which include enthesopathy, represent a­­ considerable socioeconomic burden, with an estimated annual cost in healthcare and indirect loss of wages of $850 billion. Despite its high prevalence, the cell signaling mechanisms that contribute to its pathogenesis remains unknown. Consequently, there are no disease-modifying therapies at present for enthesopathy and orthopedic surgery is the only treatment option.
 
Technology Overview
Johns Hopkins researchers have generated two independent mouse models of enthesopathy pathogenesis: a semi-Achilles tendon transection model (SMTS) and a dorsiflexion immobilization model (DI). The role of TGF-β in musculoskelatal disease has drawn increasing attention in recent years, where activated TGF-β has been shown to recruit mesenchymal stromal/stem cells (MSCs) to maintain tissue homeostasis. The researchers have shown that TGF-ß was activated in tendon-bone insertions in both the SMTS and DI models. Their work suggests that inhibition of elevated levels of active TGF-ß could serve as potential therapy.
 
Stage of Development
The inventors have generated two mouse models that reproduce enthesopathy pathogenesis. The researchers have shown that high concentrations of active TGF-ß in these models led to excessive vessel formation, bone deterioration and fibrocartilage calcification, thereby contributing to enthesopathy. Conversely, treatment of the SMTS mice with a neutralizing monoclonal antibody against TGF-β (1D11) attenuated the enthesopathy pathology compared to mice injected with a vehicle antibody. These models may provide valuable tools for screening potential therapeutics targeting the TGF-ß pathway involved in enthesopathy.

Publications
J Clin Invest. 2018;128(2):846–860
 

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