impact factor

Specific organs


The “elusive DMOAD”: Aggrecanase inhibition from laboratory to clinic

1, 2


  1. Rush University Medical School, Department of Medicine, Division of Rheumatology, Chicago IL, USA.
  2. Guangzhou Institutes of Biomedical Health, Chinese Academy of Sciences, Guangzhou, China.

2019 Vol.37, N°5 ,Suppl.120
PI 0130, PF 0134
Specific organs

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PMID: 31621572 [PubMed]

Received: 17/09/2019
Accepted : 17/09/2019
In Press: 15/10/2019
Published: 15/10/2019


From the time of their discovery in 1999, the aggrecanases, and ADAMTS-5 in particular, have been heavily investigated as targets for disease-modifying osteoarthritis drug (DMOAD) development. Here, we provide a brief narrative review of the discovery efforts to target these enzymes, and how this led to the current ongoing programmes that hold promise for the future. We discuss a comparison of inhibition of collagen breakdown versus inhibition of aggrecan breakdown. We then summarise existing programmes that target ADAMTS-5, including small molecule inhibitors, monoclonal neutralising antibodies and nanobodies, and gene editing technologies. We also briefly discuss the potential analgesic effects this strategy may offer in addition to its joint-protective effects.

Rheumatology Article