RESEARCH POSTER PRESENTATION DESIGN © 2015 www.PosterPresentations.com Lew Lim, PhD, MBA Vielight Inc, Toronto, ON, Canada Photobiomodulation Pathway Map in addressing Alzheimer's Disease with Vielight Neuro Gamma Presented at: Alzheimer’s Association International Conference, July 14-18, 2019 Key Parameters: • 810 nm Near Infrared Light • Pulse rate of 40 Hz • Targeting the Default Mode Network • 20 min/day/6-day-week, home-use • Total energy dose of 240 J Delta Theta Alpha Beta Gamma Frequency band 0 2 4 6 8 10 12 Absolute Power spectrum Active Sham Weeks Change in ADAS-cog from baseline -12 -10 -8 -6 -4 -2 0 2 4 6 8 PBM UC Single Intervention with Vielight Neuro Gamma Cellular-level Effects Factors affecting Alzheimer’s Disease Clinical Outcomes as at June 2019 M2 Microglia 2,3 Mitochondria 5 Interfacial Water Layer 8 Β-amyloid oligomers 2 Tau – neurofibrillary tangles 3 Memory encoding 14 Inflammation 10 Blood circulation & oxygenation 9 Neurogenesis & synaptogenesis 12 Saltmarche et al, 2017 15 • Journalized reports • MMSE • ADAS-cog Chao, 2019 16 • ADAS-cog • NPI • fMRI • ASL Zommorodi, et al, 2019 17 • EEG, Power spectrum • Connectivity Electron Transport Chain 6 Heat-gated ion channels 5 Positioning on the Default Mode Network Network and interneurons 14 Neurons Stem/progenitor cells 12 Microtubules 4 Cytochrome C Oxidase 6 ATP ROS cAMP AP1 5 NO 9 COX-2 inhibitor 10 Altered NFKB 11 BDNF 13 References 1. ClinicalTrials.gov. Neuro RX Gamma - Pivotal Phase. Accessed July 2019: https://clinicaltrials.gov/ct2/show/NCT03484143. 2. Iaccarino HF, Singer AC, Martorell AJ et al. Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature. 2016;540(7632):230-235. 3 Adaikkan C, Middleton S.J, Marco A, et al. Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection. Neuron 2019; 102:929–943. 4. Albrecht-Buehler G. Cellular infrared detector appears to be contained in the centrosome. Cell Motil Cytoskeleton. 1994;27(3):262-71. 5. Hamblin, M.R. Photobiomodulation for Alzheimer’s Disease: Has the Light Dawned? Photonics 2019; 6:77. 6. Cooper CE, Cope M, Springett R, et al. Use of Mitochondrial Inhibitors to Demonstrate That Cytochrome Oxidase Near-Infrared Spectroscopy Can Measure Mitochondrial Dysfunction Noninvasively in the Brain. Br. J. Pharmacol. 1999; 19:27–38. 7. Karu TI. Multiple roles of cytochrome c oxidase in mammalian cells under action of red and IR-A radiation. IUBMB Life. 2010; 62:607–610. 8. Sommer AP. Mitochondrial cytochrome c oxidase is not the primary acceptor for near infrared light—It is mitochondrial bound water: The principles of low-level light therapy. Ann. Transl. Med. 2019 7:S13. 9. Lee HI, Lee SW, Kim SY, et al. Pretreatment with light-emitting diode therapy reduces ischemic brain injury in mice through endothelial nitric oxide synthase-dependent mechanisms. Biochem. Biophys. Res. Commun. 2017; 486:945–950. 10. Lim W, Kim J, Kim S, et al. Modulation of lipopolysaccharide-induced NF- kappaB signaling pathway by 635 nm irradiation via heat shock protein 27 in human gingival fibroblast cells. Photochem. Photobiol. 2013; 89:199–207. 11. Yamaura M, Yao M, Yaroslavsky I, et al. Low level light effects on inflammatory cytokine production by rheumatoid arthritis synoviocytes. Lasers Surg. Med. 2009; 41:282–290. 12. Xuan W, Vatansever F, Huang L., et al. Transcranial low-level laser therapy enhances learning, memory, and neuroprogenitor cells after traumatic brain injury in mice. J. Biomed. Opt. 2014; 19:108003. 13. Meng C, He Z and Xing D. Low-Level Laser Therapy Rescues Dendrite Atrophy via Upregulating BDNF Expression: Implications for Alzheimer’s Disease. J. Neurosci. 2013; 33:13505–13517. 14. Palop JJ, Mucke L. Network abnormalities and interneuron dysfunction in Alzheimer disease. Nat Rev Neurosci. 2016; 17(12):777-792. 15. Saltmarche AE, Naeser MA, Ho KF, et al Significant Improvement in Cognition in Mild to Moderately Severe Dementia Cases Treated with Transcranial Plus Intranasal Photobiomodulation: Case Series Report. Photomed. Laser Surg. 2017;35:432–441. 16. Chao LL. Effects of Home Photobiomodulation Treatments on Cognitive and Behavioral Function, Cerebral Perfusion, and Resting-State Functional Connectivity in Patients with Dementia: A Pilot Trial. Photobiomodul. Photomed. Laser Surg. 2019; 37:133–141. 17. Zomorrodi R, Loheswaran G, Pushparaj A & Lim L. Pulsed Near Infrared Transcranial and Intranasal Photobiomodulation Significantly Modulates Neural Oscillations: a pilot exploratory study. Scientific Reports. 2019; 9:6309. The synopsis of this poster is available at https://vielight.com/alzheimers-disease-photobiomodulation-aaic- poster / Contact: Lew Lim: [email protected]