Near Infrared Chronic Intracranial Illumination for Neuroprotection in Parkinson's Disease
Research Grant, 2013
Objective/Rationale: † † † † † ††
The treatment of Parkinsonís Disease (PD) is based on medication and on surgical procedures. These therapies alleviate symptoms but do not change the evolution of the disease, which is a progressive degeneration of the neurons producing dopamine in the brain. This degeneration is in part due to an abnormal functioning of the mitochondrias that produce energy in these neurons. There is evidence that infrared light can counteract this mitochondrial dysfunction.†
Project Description: † † † † † ††
We will develop a prototype to deliver continuously into patientsí brains infrared light to slow down the loss of these dopaminergic neurons by improving their mitochondrial function. Human application requires checking the safety of the invented devices in laboratory pre-clinical models. An implantable prototype is being assembled from parts already made by industrial companies for deep brain stimulation. It will be implanted in models to check the safety of the surgical procedure and the long term tolerance of this device. The proof of principle of the therapeutic effect also has to be made. We will implant the device in models rendered parkinsonian by administration of the neurotoxin MPTP and observe the evolution of this parkinsonian syndrome under the effect of this intracranial illumination.
Relevance to Diagnosis/Treatment of Parkinsonís Disease: † † † † † † † † † ††
We have obtained previous evidence that infrared light protects dopaminergic neurons against MPTP in pre-clinical models. In this study we will extend this observation to models closer to human PD. The design of the study is aimed at providing a strong evidence of the neuroprotective effect, suggesting that we might have at hand a curative therapy, which has not been observed yet.
Anticipated Outcome: † † † † †
This experiment will confirm that infrared illumination is neuroprotective for neurons against MPTP, and therefore that it could be curative against PDís neurodegenerative process. It will provide data about the mechanism of action and the dose-efficiency relationship before considering a human clinical trial in PD patients. It will help testing the validity of our prototype and prepare the development and submission of a human clinical trial to explore its therapeutical validity.
To develop and test a method to protect the brain against the degeneration of dopamine nigral cells, we used a toxin which destroys nigral neurons (MPTP) by disturbing the function of mitochondria, energy producers for the neurons. MPTP treated pre-clinical were used to develop a device, implantable in the brain, to deliver near infra-red (NIR) light to nigral neurons. We found that NIR stimulation protected nigral cells against the effects of MPTP and the appearance of the Parkinsonian symptoms in a subset of MPTP treated models. We plan to build a prototype of a clinically feasible device to be implanted at early stages of Parkinsonís disease.†
Posters and Publications
1. El Massri N, Johnstone DM, Peoples CL,†Moro C, Reinhart F, Torres N, Stone J,†Benabid†AL, Mitrofanis J. The effect of different doses of near infrared light on dopaminergic cell survival and gliosis in MPTP-treated mice. Int J Neurosci. 12/2014
2. Reinhart F, Massri NE, Darlot F, Torres N, Johnstone DM, Chabrol C, Costecalde T, Stone J, Mitrofanis J,†Benabid†AL,†Moro C. 810nm near-infrared light offers neuroprotection and improves locomotor activity in MPTP-treated mice. Neurosci Res. 11/2014
3. Johnstone DM, el Massri N,†Moro C, Spana S, Wang XS, Torres N, Chabrol C, De Jaeger X, Reinhart F, Purushothuman S,†Benabid†AL, Stone J, Mitrofanis J. Indirect application of near infrared light induces neuroprotection in a mouse model of parkinsonism - an abscopal neuroprotective effect. Neurosci. 08/2014
4. Johnstone Dm, Coleman Ka, Moro C, Torres N, Eells Jt, Baker Ge, Ashkan K, Stone J, Benabid Al, Mitrofanis.The potential of light therapy in Parkinson's disease. J ChronoPhysiol Therapy 2014:4, 1-14
5.†Moro C., †Massri N., Torres N., Ratel D., De Jaeger X., Chabrol C., Perraut F., Bourgerette A., Berger M., †Purushothuman S., Johnstone D., Stone J., Mitrofanis J., Benabid A.L.. Photobiomodulation inside the brain: a novel method of applying near-infrared light intracranially and its impact on dopaminergic cell survival in MPTP-treated mice. †J. of Neurosurgery 10/2013
6. Moro C., Torres N., El Massri N., Ratel D., Johnstone D., Stone J., †Mitrofanis J., †Benabid A.L. Photobiomodulation preserves behavior and midbrain dopaminergic cells from MPTP toxicity: evidence from two mouse strains. †BMC Neuroscience 03/2013
Professor of Anatomy at University of Sydney
Location: Sydney, Australia
Chairman of the Board at The Edmond J. Safra Biomedical Research Center, Clinatec Institute
Location: Grenoble, France