Near‐infrared light is neuroprotective in a monkey model of <scp>P</scp>arkinson disease

TLDR

The study aimed to determine if near‑infrared light therapy reduces clinical symptoms and provides neuroprotection in a subacute MPTP monkey model of Parkinson’s disease. An optical fiber delivering 670‑nm near‑infrared light was implanted in the midbrain of macaques, which received MPTP injections over 5–7 days with concurrent illumination, followed by a 3‑week survival period during which clinical, behavioral, and histological assessments were performed. Near‑infrared light markedly reduced clinical and behavioral deficits, preserved dopaminergic neurons, and was non‑toxic, demonstrating therapeutic efficacy in the primate Parkinson’s model. Published in Annals of Neurology 2016;79:59–75.

Abstract

Objective To examine whether near‐infrared light (NIr) treatment reduces clinical signs and/or offers neuroprotection in a subacute 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) monkey model of Parkinson disease. Methods We implanted an optical fiber device that delivered NIr (670nm) to the midbrain of macaque monkeys, close to the substantia nigra of both sides. MPTP injections (1.5–2.1mg/kg) were made over a 5‐ to 7‐day period, during which time the NIr device was turned on. This was then followed by a 3‐week survival period. Monkeys were evaluated clinically (eg, posture, bradykinesia) and behaviorally (open field test), and their brains were processed for immunohistochemistry and stereology. Results All monkeys in the MPTP group developed severe clinical and behavioral impairment (mean clinical scores = 21–34; n = 11). By contrast, the MPTP‐NIr group developed much less clinical and behavioral impairment (n = 9); some monkeys developed moderate clinical signs (mean scores = 11–15; n = 3), whereas the majority—quite remarkably—developed few clinical signs (mean scores = 1–6; n = 6). The monkeys that developed moderate clinical signs had hematic fluid in their optical fibers at postmortem, presumably limiting NIr exposure and overall clinical improvement. NIr was not toxic to brain tissue and offered neuroprotection to dopaminergic cells and their terminations against MPTP insult, particularly in animals that developed few clinical signs. Interpretation Our findings indicate NIr to be an effective therapeutic agent in a primate model of the disease and create the template for translation into clinical trials. ANN NEUROL 2016;79:59–75