C-1101 multi-protein platelet and plasma-derived therapeutic to treat chronic lumbosacral radiculopathy.

INTRODUCTION: Intervertebral disc disease (IVDD) leads to chronic lumbosacral radiculopathy (LSR) with nerve root compression resulting in numbness and low back pain. The aim was to evaluate therapeutic and immunomodulatory potential of multi-protein platelet and plasma-derived biologic (C-1101) to alter inflammatory mediators and gene expression in IVDD. METHODS: In aim 1, intervertebral discs and dorsal root ganglia (DRG) were harvested from female ovine lumbar spines (n = 6). Annulus fibrosus (AF), nucleus pulposus (NP) and DRG were dissociated to form single-cell suspensions. Cells were plated (100,000 cells/well, 24-well plates) and subjected to 4 treatments, 24 h (non-stimulated, IL-1β+TNF-α, IL-1β+TNF-α+C-1101, IL-1β+TNF-α+vehicle). Cells were washed, cultured 24 h, and media evaluated for cytokine secretion (n = 14) by ovine multiplex immunoassay. mRNA was collected from cells and sequencing performed via Illumina-based platform. In aim 2, peripheral neuropathy was induced (paclitaxel) in male C57Bl6/J mice who were treated intravenously with C-1101 or vehicle. Mice were assessed via acetone cooling for allodynia and plasma evaluated for cytokines. RESULTS: C-1101 elicited cytokine release from ovine AF and NP cells but not DRG. Gene expression analyses revealed upregulation of cell replication and translation pathways but downregulation of inflammatory (namely, interferons), extracellular matrix and cell signaling pathways in AF/NP, with upregulation of translation and ribosome activity in DRG. C-1101 reduced allodynia and transiently induced elevated plasma IL-1β in murine peripheral neuropathy. DISCUSSION: Functional reduction in pain sensation with C-1101 was observed in murine peripheral neuropathy, indicating potential therapeutic efficacy. C-1101 induced a mixed inflammatory response in cultured cells, warranting further investigation of mechanism.