An international clinical trial, is investigating whether infrared light can improve symptoms of Parkinson's disease. The experimental results, based on preclinical studies, indeed suggest that brain illumination in the near infrared is likely to slow down this neurodegenerative disease.
Hamilton, Mitrofanis and others had previously reported that wearing headphones equipped with infrared LEDs improved quality of life, although it did not have much effect on motor symptoms.
A medical device system (called Ev-NIRT) has been developed by the French scientists and Boston Scientific Corporation, for intracerebral illumination at 670 nm of the black substance pars compacta (SNpc), and will be tested in this pilot study.
Researchers will assess the feasibility and tolerance of surgery and brain illumination using the Ev-NIRT medical device, in a group of 7 patients with Parkinson's disease in whom the innovative medical device will be implanted. The patients will be followed for 4 years.
The device will emit pulses at a wavelength of 670 nm for one minute, with a periodicity of 150 Hz. This burst of pulses will be followed by five minutes of rest.
The team, led by neurosurgeon Alim-Louis Benabid of the Clinatec Institute, hopes that exposing this area of the brain to infrared light will protect cells from death. Benabid, along with Pierre Pollak, are the pioneers who developed deep brain stimulation (DBS) in 1987. DBS works by sending electrical impulses into the brain. This invention has changed the lives of thousands of patients, but it has long term side effects.
About ten years ago, John Mitrofanis, a neuroanatomist at the University of Sydney, spent a year studying DBS with Benabid with the aim of creating a similar concept, but using infrared light. Mitrofanis was inspired by infrared headsets, used in the Parkinson's community.
Benabid and Mitrofanis, however, felt that light from outside the skull would not penetrate deep enough and that an implantable device had to be created. In 2017, in collaboration with researcher Cécile Moro, they injected 20 macaques with a neurotoxin present in certain recreational drugs (MPTP) and known to cause the symptoms of Parkinson's disease. Scientists exposed nine macaques to near infrared in the midbrain region using an implanted device.
The French study will follow 14 patients with early-stage Parkinson's disease for 4 years, seven of whom will be treated periodically with 670 nanometer pulses of light delivered to the brain via a thin laser diode cable. The other seven patients will not be operated on; an ethics review committee has in fact decided not to subject them to surgery without the possibility of benefit.
Some Parkinson's researchers are skeptical. No one has shown why exposure to infrared should have an effect on cells that never see daylight. Neurons do not have a chlorophyll-based metabolism. Much of the encouraging results seen so far may be the result of the placebo effect, skeptics say.
There are three main hypotheses to explain how photomodulation works.
The first recalls that molecules sensitive to light in the body called chromophores are excited by photon stimulation. We now know that hemoglobin, myoglobin and COX are the only 3 chromophores in mammalian tissues capable of absorbing near infrared light (wavelength 600 to 900 nm). However, there is no clear mechanism of action linking these chromophores to the increased ATP synthesis which is observed under light stimulation.
The second hypothesis explains that the production of mitochondrial energy is the effect of a reduction in the intra-mitochondrial viscosity of water induced by the near infrared. the reduction in near infrared mediated viscosity decreases the friction that opposes the rotation of ATP synthase and results in a "smoother" rotation of the ATP synthase machinery. This theory is supported by the fact that increases in cellular ATP level are immediate after near infrared stimulation.
A third hypothesis suggests that the photoabsorbent pyropherophorbide-a (P-a) metabolite of dietary chlorophyll may facilitate light energy production processes in animals. In the experiments, ATP levels increased only in groups where P-a and near infrared light were co-administered, and not in those where P-a or near infrared were administered in isolation. Given the multiplicity of these competing theories, it is possible that the near infrared exerts its modulatory effects through several mechanisms instead of just one.
The main aim of this new clinical study is to prove that the implant is safe, says Benabid, but the researchers will also assess the progression of the disease. “This must lead to a great improvement,” he says. "There would be no reason to have extensive surgery for only slight improvement."
The major problem with all neuroprotection trials in Parkinson's disease is that diagnosis appears to occur after more than 50% of the dopamine-producing cells have disappeared. Unless the improvement is huge, the signal will be too weak to be detected.
The team will also be looking for clinical benefits. But because researchers assess symptoms of Parkinson's disease by observing patients performing specific tasks, the assessments are largely subjective and symptoms vary over time; everyone has good days and bad. Since the control group will not undergo surgery, it will be particularly difficult to rule out placebo effects.