Chronic intracranial photobiomodulation for Parkinson's disease : a 15-year story from bench to bedside

Photobiomodulation (PBM) utilizes light within the red-to-near-infrared range (λ = 600 to 1000nm) to modulate cellular activity and enhance tissue resilience. Over the past fifteen years, our group has demonstrated, in several preclinical models of Parkinson’s disease (PD), that PBM can significantly reduce dopaminergic neurodegeneration. These effects appear to arise from the activation of intrinsic self-protective and repair mechanisms, promoting neuronal survival in conditions of stress or injury. Building upon this robust preclinical foundation, we initiated a first-in-human proof-of-concept clinical trial (NCT04261569) involving fourteen patients with early-stage PD. Seven participants received intracranial PBM treatment through a dedicated implantable light-delivery device. All participants are followed for four years with standardized motor and neurological assessments, as well as dopaminergic imaging, to monitor disease progression. After one year, no adverse events have been reported, confirming the safety and tolerability of the intracranial PBM approach. Preliminary one-year outcomes suggest stabilization of motor symptoms in the PBM-treated group, contrasting with the expected decline in untreated PD patients. Although early, these findings indicate that PBM may offer a novel disease-modifying therapeutic strategy. This work highlights the translational potential of light-based neuromodulation and its promise as a safe, nonpharmacological intervention for neurodegenerative diseases, paving the way for larger-scale clinical validation.