The “elusive DMOAD”: Aggrecanase inhibition from laboratory to clinic
A.-M. Malfait1, M.D. Tortorella2
- Rush University Medical School, Department of Medicine, Division of Rheumatology, Chicago IL, USA. email@example.com
- Guangzhou Institutes of Biomedical Health, Chinese Academy of Sciences, Guangzhou, China.
2019 Vol.37, N°5 ,Suppl.120
PI 0130, PF 0134
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PMID: 31621572 [PubMed]
Accepted : 17/09/2019
In Press: 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.