Transcranial Near-Infrared Laser Therapy for Stroke: How to Recover from Futility in the NEST-3 Clinical Trial
Development of drugs and devices for the treatment of stroke is not exempt from current translational research standards, which include Stroke Treatment Academic Industry Roundtable (STAIR) criteria and RIGOR guidelines. Near-infrared laser therapy (NILT) was developed to treat stroke in an era when STAIR criteria were not adhered to, thus NILT was not optimized in multiple species, nor was it optimized for efficacy across barriers in translational animal models before proceeding to expensive and extensive clinical trials. Moreover, the majority of rodent studies did not adhere to RIGOR guidelines. This ultimately led to failure in the NeuroThera Effectiveness and Safety Trial-3. Because NILT remains a promising therapeutic approach to treat stroke, we designed a systematic study to determine laser light penetration profiles across the skull of four different species with increasing skull thickness: mouse, rat, rabbit, and human.
Our study demonstrates that NILT differentially penetrates the skulls. There is especially extensive attenuation of light energy penetration across the human calvaria, compared with animal skulls, which suggests that the power density setting used in stroke clinical trials may not have optimally stimulated neuroprotection and repair pathways. The results of our study suggest that NILT cannot be sufficiently optimized in “small” animals and directly translated to humans because of significant variances of skull thickness and penetration characteristics across species. NILT neuroprotection should be further studied using a research design that endeavors to incorporate human skull characteristics (thickness) into the development plan to increase the probability of success in stroke victims.
KeywordsAcute ischemic stroke Alzheimer’s disease Amyloid Behavior Laser therapy Mitochondria Neuroprotection NEST trials NILT Parkinson’s disease Translational science Traumatic brain injury Toxicity Victim Unmet clinical need
Conflict of Interest Statement
This study utilized a K-Laser model K-1200 device. K-Laser, Inc. did not have an editorial influence on the study design or scientific content of this article.
Disclosures and Acknowledgments
Dr. Lapchak serves as editor-in-chief of the Journal of Neurology & Neurophysiology and associate editor of Translational Stroke Research. The scientific content of this work was not directly supported by the National Institutes of Health or any other funding source external to Cedars-Sinai Medical Center. He was supported in part by a U01 translational research grant NS060685. Paul D. Boitano has no disclosures.
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