BioCentury
ARTICLE | Distillery Therapeutics

Neurology

September 10, 2018 7:32 PM UTC

Patient sample and mouse studies suggest inhibiting the JAK/STAT1 pathway, the interaction between MCP-1 and CCR2, or phagocyte activation could help treat Rasmussen encephalitis. In postmortem brain samples from patients, levels of phosphorylated STAT1 and MCP-1 and the number of activated phagocytes were higher than in samples from patients with non-neurological diseases. In a mouse model of Rasmussen encephalitis, inhibiting STAT1 activity with the JAK-1/JAK-2 inhibitor Jakavi ruxolitinib or a tool compound JAK-2 inhibitor decreased motor deficits and increased synaptic density compared with vehicle. Also in the model, neuron-specific STAT1 or MCP-1 knockout, treatment with a mAb against the MCP-1 receptor CCR2, or inhibiting phagocyte activation with generic antibiotic minocycline decreased motor deficits and increased synaptic density compared with normal STAT1 and MCP-1 expression, an isotype control antibody or vehicle, respectively. Next steps could include identifying and testing other STAT1 or MCP-1 inhibitors in the model.

Incyte Corp. and Novartis AG market Jakavi for myeloproliferative disorder and have the compound in Phase III testing for graft-versus-host disease (GvHD), Phase II testing for breast cancer, colorectal cancer and leukemia and Phase I testing for myelodysplastic syndrome (MDS)...