Jackson Streeter M.D. August 2004 ECI Conference Jackson Streeter M.D. August 2004 Tate to begin…intro group, etc.

Scope of problem One stroke every 45 seconds in North America 1.8 million new strokes per year in industrialized countries One FDA approved treatment is tPA Over $20 billion direct costs in USA Number 3 killer in USA Less than 5% of patients receive any treatment other than rehab Jackson – in the time we’ve been here, ____people have had a stroke

Stroke facts When diagnosed 15% hemorrhagic 85% ischemic Hemorrhagic are the most severe with 50% patients presenting within 3 hours Only ischemic are “treatable” with tPA. Hemorrhagic vs ischemic pictures…

Time – the critical element of stroke treatment The untreated tPA I made this up, can someone please come up with actual numbers?

Technology – How does it work? Specific infrared wavelength Transmits through skull to cortex Absorbed by a known molecular receptor within mitochondria Increases mitochondrial viability and activity (NOT removing clot) Stimulates over 1000 metabolic reactions Examples: increase ATP, neurotransmitters, decrease apoptosis Neuroprotection Neurogenesis Improve neurological function and decrease infarct size after ischemic insult Jackson -

Mechanism of Action Specific infrared wavelength: Absorbed by Cu Centers in cytochrome C oxidase Enhance mitochondrial viability and activity (increase ATP) Jackson - Eells, J. T. et al. Proceedings National Academy of Science 2003; 100:3439-3444 T.I. Karu "Low power laser therapy". In: Biomedical Photonics Handbook. Ch. 48,  Editor-in-chief Tuan Vo-Dinh, Boca Raton: CRC Press. 2003.

Effects of Increased Mitochondrial Activity and Viability DNA & RNA Synthesis Neurotransmitter Synthesis Calcium homeostasis Decrease Apoptosis and Cell Death Heme Synthesis Estrogen Synthesis Free radical detoxification ATP synthesis Over 1000 metabolic reactions

Working in man – our preclinical and clinical plans STAIR1 Criteria Appropriate models Functional tests External lab validation “Exposure” Time window Additional Effective in Human Neurons in vitro Able to deliver required amount of energy in man Work in a clot model (2nd Species) 1 Stroke Therapy Academic and Industry Roundtable (STAIR) Recommendations for Standards Regarding Preclinical Neuroprotective and Restorative Drug Development. Stroke 1999; 30:2752-2758

Sprague Dawley Subjects

MCA Occlusion

Preclinical – Rat Model Using recommended protocol(s) for transient and permanent occlusion Induced cerebral ischemia in rats 24 hour delay before treatment Filament

Transmission 10mW/cm2 2min 808nm cw

Rotational Test

Balance Beam Test

Post Surgery

Treatment at 24 hours post stroke Laser treatment 10mW/cm2 2min 1.2J/cm2 808nm cw Outcome measures: Neurological function Not a helpful slide

1 ANM-ZC05-027 12/03 - Weighted average of 4 individual tests Results Significant at p<0.001* 1 ANM-ZC05-027 12/03 - Weighted average of 4 individual tests

Questions?