AMG 487 → Parkinsons Disease Neuropsychiatric Symptoms

Original Indication

Investigated for inflammatory diseases (e.g., rheumatoid arthritis) as a CXCR3 antagonist.

Proposed New Indication

Repurposing AMG 487 to mitigate neuropsychiatric symptoms (e.g., apathy, depression, cognitive impairment) in Parkinson's Disease by targeting neuroinflammation.

Proposed Mechanism

Targets: CXCR3, Neuroinflammation

AMG 487, as a CXCR3 antagonist, is hypothesized to block the binding of CXCR3 ligands (like CXCL10, CXCL11, CXCL9) to CXCR3 receptors on immune cells (T lymphocytes, NK cells, microglia). This inhibition would reduce the migration and infiltration of these inflammatory cells into the central nervous system, thereby dampening neuroinflammation. By attenuating the neuroinflammatory processes, it could alleviate neuronal damage and dysfunction contributing to neuropsychiatric symptoms in Parkinson's Disease.

Evidence

Level: In silico / Pre-clinique (based on mechanistic understanding of CXCR3 in neurodegeneration and inflammation)

Source: PMID 40310263 highlights chemokine receptors (CXCR3, CXCR5) as advantageous therapeutic targets in neurodegenerative diseases like Parkinson's. PMID 41884484 reviews the role of CXCL10/CXCR3 in inflammatory processes, providing mechanistic support for targeting this axis.

Reference: PubMed 40310263

Repurposing Score