Dr. Wee Yong, Dr. Chang-Chun Ling, and collaborators at the University of Calgary have generated a series of fluorinated glucosamine analogs that inhibit the production of chondroitin sulfate proteoglycans (CSPG)s. In neurological disorders like multiple sclerosis, CSPGs are upregulated, which increase the immune response and act as a barrier to remyelination. In vitro and in vivo studies have demonstrated the novel glucosamine compounds are able to enhance oligodendrocyte precursor cell (OPC) growth, reduce T cell proliferation, and reduce CSPG production. Experimental autoimmune encephalomyelitis (EAE) mice that were given the compounds showed reduced EAE clinical severity.
AREAS OF APPLICATION
- Treatment of Multiple Sclerosis.
- Other potential areas of application include Alzheimer’s disease, traumatic brain injury, stroke, Amyotrophic Lateral Sclerosis, Huntington’s disease, Parkinson’s disease, and neuroinflammatory diseases.
- Inhibits CSPG biosynthesis and promotes natural remyelination.
- Novel glucosamine analogs have greater potency and efficacy than current compounds in blocking CSPG biosynthesis.
KEY OPINION LEADER/EXPERT COMMENTS
“Agents that inhibit CSPGs should be studied further in MS, as they have the potential to favourably influence multiple CNS-compartmentalized and peripheral pathways involved in MS pathophysiology.” – Amit Bar-Or, Melissa and Paul Anderson President’s Distinguished Professor, University of Pennsylvania; Nature Reviews Neurology volume 18, pages 466–475 (2022).
PUBLICATIONS AND RESOURCES
- Journal publications:
- Stephenson EL et al. (2019). Targeting the chondroitin sulfate proteoglycans: evaluating fluorinated glucosamines and xylosides in screens pertinent to multiple sclerosis. ACS Central Science 5(7): 1223-1234.
- Keough MB et al. (2016). An inhibitor of chondroitin sulfate proteoglycan synthesis promotes central nervous system remyelination. Nat Commun 7(11312).
- Researcher profile: Wee Yong
- Researcher profile: Chang-Chun Ling