Technology

Overview

PhotoThera is a medical device company whose platform technology seeks to employ penetrating near-infrared laser energy to treat a broad range of diseases and health conditions. The Company is initially focused on the treatment of ischemic stroke and is engaged in a clinical study to investigate the effect of its Transcranial Laser Therapy (TLT) when used within 24 hours of the onset of stroke symptoms.

Scientific Background

The therapeutic benefit of PhotoThera’s platform technology is derived from a process called photobiomodulation.  Photobiomodulation involves the exposure of tissues to specific wavelengths of laser energy to stimulate or inhibit cellular functions. A photochemical reaction within a targeted photoreceptor molecule generates the beneficial effects within the exposed tissues and may lead to improved clinical outcomes for the patient.  In the case of PhotoThera’s technology, TLT with near-infrared laser (NIR) energy is targeted to photoreceptor molecules within the mitochondria of living cells.¹

Mitochondria are membrane-bound organelles found within the cytoplasm of cells.  They are commonly referred to as the “powerhouse of the cell” because they are responsible for generating the vast majority of the cell’s energy supply in the form of adenosine triphosphate (ATP).  In addition, mitochondria are involved in multiple cellular regulatory processes including signaling, differentiation, growth, homeostasis, control of the cell cycle, and cell death.^2,3

Evidence suggests that the mitochondrial photoreceptor molecule in the red to near-infrared region is the enzyme, Cytochrome c Oxidase (CcO), a key enzyme in the mitochondrial electron transport chain.⁴  Energy absorption by CcO promotes electrons into an excited state. The resulting photo-excitation can result in changes in redox properties of the enzyme as well as nitric oxide (NO) release from an inhibitive position in CcO’s catalytic center.¹  As a result, a cascade of events is triggered that can promote and/or inhibit certain cellular pathways, leading to beneficial cellular effects.  These include changes in membrane electrochemical gradients and permeability, increases in production of ATP, nuclear signaling, and the inhibition of apoptosis. It is these cellular effects that may ultimately lead to clinical benefits such as improved recovery,^5-7 wound healing,⁸ tissue regeneration,⁹ decreased inflammation, or pain relief.¹⁰

Platform Technology

Cellular mitochondrial dysfunction has been increasingly identified as a critical contributor to several significant medical conditions including diabetes,¹¹ cancer,¹² obesity,¹³ ischemic stroke,¹⁴ traumatic brain injury,¹⁵ and several neurodegenerative conditions.^16-18 A common feature linking these conditions is the disruption of normal energy metabolism within mitochondria. Specifically, TLT has the ability to improve this mitochondrial energy imbalance, leading to improved cellular metabolism, mitigation of apoptosis, and activation of recovery mechanisms. 

The Company is focused on ischemic stroke as its initial clinical application.  Potential additional indications for this technology include traumatic brain injury, global cerebral ischemia, spinal cord injury, Alzheimer’s disease, Parkinson’s disease and sepsis. Preclinical investigations are ongoing in multiple areas.

References:

1.        Karu TI. Cellular mechanisms of low-power laser therapy. (Invited Paper) Proc. SPIE. 2003;5149:60-66.

2.        McBride HM, Neuspiel M, Wasiak S. Mitochondria: more than just a powerhouse. Curr. Biol. 2006; 16(14):551–60.

3.        Dubinsky JM, Brustovetsky N, LaFrance R. Protective roles of CNS mitochondria. J Bioenerg Biomembr. 2004;36(4):299-302.

4.        Karu, T.  Mechanisms of interaction of monochromatic visible light with cells. Proc. SPIE. 1995;2630, 2–9.

5.        Lampl Y, Zivin JA, Fisher M, Lew R, Welin L, Dahlof B, Borenstein P, Andersson B, Perez J, Caparo C, Ilic S, and Oron U.  Infrared laser therapy for ischemic stroke: a new treatment strategy: results of the NeuroThera Effectiveness and Safety Trial-1 (NEST-1). Stroke. 2007;38:1843 - 1849.

6.        Liang HL, Whelan HT, Eells JT, Meng H, Buchmann E, Lerch-Gaggl A, Wong-Riley M. (2006). Photobiomodulation partially rescues visual cortical neurons from cyanide-induced apoptosis. Neuroscience. 2006;139(2):639-49.

7.        Byrnes KR, Wu X, Waynant RW, Ilev IK, Anders JJ.  Low power laser irradiation alters gene expression of olfactory ensheathing cells in vitro. Lasers Surg Med. 2005;37(2):161-71.

8.        Byrnes KR, Barna L, Chenault VM, Waynant RW, Ilev IK, Longo L, Miracco C, Johnson B, Anders JJ.  Photobiomodulation improves cutaneous wound healing in an animal model of type II diabetes. Photomed Laser Surg. 2004;22(4):281-90.

9.        Eells JT, Wong-Riley MT, VerHoeve J, Henry M, Buchman EV, Kane MP, Gould LJ, Das R, Jett M, Hodgson BD, Margolis D, Whelan HT.  Mitochondrial signal transduction in accelerated wound and retinal healing by near-infrared light therapy. Mitochondrion. 2004;4(5-6):559-67.

10.     Naeser MA.  Photobiomodulation of pain in carpal tunnel syndrome: review of seven laser therapy studies. Photomed Laser Surg. 2006;24(2):101-10.

11.     Maassen JA, 't Hart LM, Ouwens DM.  Lessons that can be learned from patients with diabetogenic mutations in mitochondrial DNA: implications for common type 2 diabetes. Curr Opin Clin Nutr Metab Care. 2007;10(6):693-7.

12.     Dahm F, Bielawska A, Nocito A, Georgiev P, Szulc ZM, Bielawski J, Jochum W, Dindo D, Hannun YA, Clavien PA.  Mitochondrially targeted ceramide LCL-30 inhibits colorectal cancer in mice. Br J Cancer. 2008;15;98(1):98-105.

13.     Keijer J, van Schothorst EM. Adipose tissue failure and mitochondria as a possible target for improvement by bioactive food components. Curr Opin Lipidol. 2008;19(1):4-10.

14.     Sims NR, Anderson MF. Mitochondrial contributions to tissue damage in stroke. Neurochem Int. 2002;40(6):511-26.

15.     Singh IN, Sullivan PG, Deng Y, Mbye LH, Hall ED. Time course of post-traumatic mitochondrial oxidative damage and dysfunction in a mouse model of focal traumatic brain injury: implications for neuroprotective therapy. J Cereb Blood Flow Metab. 2006;26(11):1407-18.

16.     Zeviani M, Carelli V.  Mitochondrial disorders. Curr Opin Neurol. 2007;20(5):564-71.

17.     Petrozzi L, Ricci G, Giglioli NJ, Siciliano G, Mancuso M. Mitochondria and neurodegeneration. Biosci Rep. 2007;27(1-3):87-104.

18.     Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006;443(7113):787-95.