Towards intervertebral disc repair by using novel small molecules that regulate proteoglycan metabolism

Dr Leung, Victor Yu Leong   (Principal Investigator (PI))

Professor Chan Danny   (Co-Investigator)

Professor Cheung Kenneth Man Chee   (Co-Investigator)

Professor Li Xuechen   (Co-Investigator)

24

2014-10-01

2016-09-30

934314

Towards intervertebral disc repair by using novel small molecules that regulate proteoglycan metabolism

Degeneration, Inflammation, Intervertebral disc, Proteoglycan, Small molecules

BiochemistryDrug Discovery and Delivery

N/A

AO Foundation Research Fund

2013

Completed

IVDs are susceptible to age- or non-age related degeneration with little capacity to self-repair. IDD is associated with low back pain and is related to a loss of proteoglycan content. Our study has shown that specific synthetic small molecules in the chemical library are potent in enhancing proteoglycan production in the NP cells and in promoting IVD repair. The capacity of CSG-1 in inhibiting IL-1 mediated proteoglycan catabolism, and intervening the loss of disc function in the animal model, suggests it may potentially target key regulators involved in the pathophysiology of IDD. Our findings strongly implicate an outstanding potential of CSG-1 in developing into a new druggable agent for alleviating IDD. As it can inhibit inflammatory signals such as IL-1, CSG-1 might also have the potential in alleviating discogenic pain. To generate necessary evidence for next phase of investigation in humans, we plan to better understand the property and refine the activity of CSG-1, which is a perquisite for any drug development. 1. Determine the structure-activity relationship of CSG-1; 2. Search for derivatives of CSG-1 that display optimal efficacy; 3. Identify the protein target of CSG-1