Proposal for co-development of glycolipid therapeutics for inflammatory diseases (IBD, SLE)

Controlling inflammation by regulating T cell ganglioside content with glycolipid GlcCer containing nanoparticle formulation (GlcCer-LNP)

Advantage

  • Novel therapeutic approach with lipid nanoparticles (LNPs) containing GlcCer
  • Original T cell-directed LNPs for delivery to T cells

Background and Technology

Sphingoglycolipids such as ganglioside sphingolipids and glucosylceramide (GlcCer) are composed of a hydrophobic ceramide moiety and a hydrophilic sugar chain moiety and have the property of fusing with the cell membrane. They cluster with each other outside the cell membrane to form domains, which associate with membrane proteins and intracellularly localized signaling molecules to form functional membrane domains called lipid rafts. Gangliosides are an important component of T cells involved in the regulation of the immune system, and dysregulation of their content has been shown to be a possible pathogenesis of inflammatory diseases such as IBD and SLE.

The inventors demonstrated the relevance of glycolipids in T cells to inflammatory diseases, and found that the expression of sphingoglycolipid synthase (UGCG) is decreased in ulcerative colitis-induced mice, and that knockdown of Ugcg in T cells aggravates the pathogenesis of colitis. Then, they demonstrated that intravenous administration of GlcCer-lipid nanoparticles combined with their original T cell-directed envelope lipid nanoparticles ameliorated the pathological condition.

Data

  • Comparison of body weight change (left) and survival days (right) in mice with ulcerative colitis (UC) induced by dextran sulfate sodium (DSS), with a group treated with intravenous GlcCer-containing LNP and a control group with LNP without GlcCer.

Patent

Pending

Researchers

Masaki Nagane, Lecture, School of Veterinary Medicine, Azabu University
Takashi Nakamura, Assistant Professor, Faculty of Pharmaceutical Sciences, Hokkaido University

Development Stage

Current Stage: Animal PoC stage, in vivo therapeutic effect of GlcCer-LNP was confirmed in mouse model of ulcerative colitis.

Next stage: We are looking for partner companies that can help us demonstrate the efficacy of GlcCer-LNP in inflammatory diseases model other than IBD, such as SLE, and develop therapeutic drugs with us.

Product No. ON-03933a

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