BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: FAS receptor (CD95); CD95 ligand

August 4, 2016 7:00 AM UTC

Patient sample and mouse studies suggest inhibitors of CD95-mediated calcium signaling could help treat SLE. In patient serum and skin samples, levels of soluble CD95 ligand were higher than in samples from age-matched healthy volunteers. In activated human peripheral blood monocytes, a cell-penetrating peptide derived from the non-apoptotic, calcium-inducing domain (CID) of CD95 decreased CD95-mediated calcium signaling compared with a control CD95-derived peptide, without affecting CD95-mediated apoptosis. In a mouse model of SLE, the peptide decreased splenomegaly, kidney inflammation, mesenteric lymph node weights and cell infiltration into the spleen and kidney, and increased kidney function compared with a non-specific peptide sequence. Next steps include identifying small molecule inhibitors of the CD95-mediated calcium signaling pathway...