Light therapy can help to improve mood and strengthen the immune system, laser therapy is used in pain therapy and to accelerate wound healing. Can light pulses also protect neurons of the substantia nigra from destruction? After promising observations from animal models, several human studies are in their early stages.
When the Australian neuroanatomist Prof. John Mitrofanis learned 10 years ago that light in the near-infrared (NIR) range can protect retinal cells against toxins, he had the idea to try this in Parkinson's disease. First, his team used a mouse model of the disease to show that this light protected the dopamine-producing cells of the substantia nigra from a neurotoxin. He told this to the French neurosurgeon and physicist Alim Louis Benabid, one of the co-developers of the Deep Brain Stimulation (DBS) method, with whom he had already done research in the past.
Both of them came to the conclusion that if the light was only directed at the skull from outside, as in mice, it would not penetrate deep enough in larger animals. Benabid immediately thought of a device that would bring the impulses close to the target area.
In 2017 such a device was developed. It was implanted in nine macaques that had received a neurotoxin that causes Parkinson's disease. The implanted device applied NIR light to the midbrain. When the first monkey moved after three weeks as if nothing had ever happened, the scientists were almost euphoric. Compared to eleven macaques that had received only the neurotoxin, the light-treated animals developed fewer symptoms and 20-60% of the neurons normally attacked by the neurotoxin were preserved.
Mitrofanis and some colleagues (including one who treated her own arthritic knee with an envelope of LEDs) published a study on six Parkinson's patients last year. In these patients, wearing helmets lined with LEDs improved facial expression, auditory processing, participation in conversations, sleep quality, and motivation. Unfortunately, no major effect on motor skills was observed. One of the patients stated that "When I miss a day session, I slowly change. Bad dreams return, my tolerance level drops significantly and my lethargy increases significantly".
At the University of Sydney, a study is planned with 120 patients wearing a more sophisticated helmet. At the University of Florida, too, the effect of externally applied NIR light versus "sham" light on behavior and motor skills will soon be investigated in 24 randomized patients. Although Dawn Bowers, the neuropsychologist who will lead this trial, is excited, she herself expresses uncertainty as to whether a transcranial procedure can penetrate deep enough to achieve really substantial improvements. She is more hopeful about the more invasive version of the implant.
The first study of this kind will be started this autumn by Dr. Benabid in France and will follow 14 patients with early-stage Parkinson's disease for 4 years. Seven of them will be treated at regular intervals with light pulses of 670 nanometres, which are delivered to the brain via a thin laser diode cable. The initial priority here will be to demonstrate the safety of the implant and evaluate the progress of the disease. Dr. Benabid himself says: "The effect must be great. There is no reason to perform extensive surgery for only a slight improvement". One difficulty will be to detect the protective effect if any.
The scientists will measure the amount of dopamine-producing neurons using standard imaging techniques. But another internationally renowned Parkinson's specialist, Professor Dave Sulzer of Columbia University’s Irving Medical Centre, has several obstacles to consider: because there are no biomarkers that are well associated with changes in the symptom burden of Parkinson's, "we need to monitor behavior" he explained. The researchers will also look at clinical benefits. But these assessments will always remain subjective because scientists classify Parkinson's symptoms according to how patients perform specific tasks. In addition, everyone who has been treated experiences fluctuations in their daily form.
More importantly: "The main problem with all neuroprotection studies in Parkinson's disease is that the diagnosis seems to be made when more than 50% of the dopamine-producing cells have gone down". If the improvement is not enormous, "the signal might be too small to detect," Prof. Sulzer says.
In addition, a placebo-controlled design would be difficult or unacceptable in such a situation. The ethics committee has therefore refused to impose a sham procedure on the other seven patients. Skeptics criticize the approach because it is unclear how this can affect cells that are so deep in the brain that they normally never see the light.
However, Sulzer believes that the absence of a clear mechanism of action is no reason to dismiss the therapeutic approach. He points out that we do not understand this in many situations.
Some suspect that light stimulates the energy-producing mitochondria of neurons. In vitro experiments have shown that light activates the enzyme cytochrome c oxidase on the mitochondrial membranes. This increases cellular energy production, which in turn could increase blood flow and stimulate cells to produce certain neuroprotective proteins and growth factors more efficiently.1
References:
1. Sinha, G. Trials begin for a new weapon against Parkinson’s: light. Science 369, 1415–1416 (2020).