Study Rationale: Glunomab is a monoclonal antibody that inhibits a toxic interaction between two proteins recently determined to be involved in the pathology of Parkinson’s disease (PD). Because its main target is present on the endothelial cells that line blood vessels, Glunomab does not need to cross the blood-brain barrier to exert its effect on the central nervous system (CNS), a major therapeutic advantage. Preliminary data has demonstrated that Glunomab reduced the activation of the brain’s immune cells, called microglia, and the infiltration of T cells into the CNS. This action subsequently prevented dopaminergic neuron degeneration and behavioral deficits in an alpha-synuclein preclinical mouse model of PD.
Hypothesis: We hypothesize that Glunomab acts on vascular endothelial cells to alter the permeability of the blood-brain barrier and the migration of inflammatory cells into the brain, and that this action produces a therapeutic diminishment of neurodegeneration.
Study Design: In this two-part program, we will use two complementary gold-standard preclinical mouse model of PD to confirm the efficacy of Glunomab in two independent laboratories using new efficacy endpoints, validate the absence of sex impact on treatment efficacy, assess delayed-treatment starts to target different stages in PD progression, perform a dose-response study and identify new biomarkers of target engagement.
Impact on Diagnosis/Treatment of Parkinson’s disease: Glunomab has a remarkable potential and we anticipate that these experiments will provide a strong proof of concept for its potential use as a treatment for PD and will accelerate its clinical testing as a disease-modifying drug.
Next Steps for Development: Standard studies of Glunomab’s pharmacokinetic profile, safety and toxicity are underway. If successful, our program will benefit from these ongoing regulatory studies and demonstration of manufacturing quality control, which will support the drug’s investigational new drug (IND) application and future Phase 1 and later clinical studies.