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

2. 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

3. 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…

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

5. 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 -

6. 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:
T.I. Karu "Low power laser therapy". In: Biomedical Photonics Handbook. Ch. 48,  Editor-in-chief Tuan Vo-Dinh, Boca Raton: CRC Press

7. 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

8. 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:

9. Sprague Dawley Subjects

10. MCA Occlusion

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

12. Transmission
10mW/cm2 2min 808nm cw

13. Rotational Test

14. Balance Beam Test

15. Post Surgery

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

17. 1 ANM-ZC05-027 12/03 - Weighted average of 4 individual tests
Results
Significant at p<0.001*
1 ANM-ZC /03 - Weighted average of 4 individual tests

18. Questions?