A double-blind, placebo-controlled randomized evaluation of the effect of the Erchonia EML and the Erchonia THL laser devices on Parkinson’s disease clinical study protocol

Theory of mechanism of operation:

Parkinsonism is a clinical syndrome defined by diminished facial expression, stooped posture, slowness of voluntary movement, festinating gait, and tremors.

Parkinson disease (PD) is found in individuals with progressive Parkin- sonism and is diagnosed based on clinical assessment and diagnostic exclusion. Parkinson disease is associated with the degeneration of dopaimnergic neurons of the substantia nigra, which results in a reduction in the strital dopamine content.

Therefore, the severity of the disorder is correlated to the deficiency of dopamine. Degenerative changes have been observed in other brainstem nuclei, specifically the locus caeruleus and the dorsal metanucleus of the vagus.

The common therapeutic regimen is the administration of levodopa (LDOPA), which is used in the symptomatic treatment of PD, Parkinsonian syndrome, and symptomatic Parkinsonism resulting from carbon monoxide intoxication and/or manganese intoxication.

Neurons of the substantia nigra protrude into the corpus striatum where they release the neurotransmitter dopamine. The loss of striatal dopamine is the principle effect associated in PD. The exact mechanism remains unknown; however, it is strongly believed that genetic and environmental factors play a role.

The overall pathology of PD arises from the degeneration and death of neurons of the substantia nigra. Several pathophysiologic mechanisms, such as oxidative stress, mitochondrial dysfunction, abnormalities of the ubiquitin proteasome system, and abnormal folding and degradation of major intracellular proteins, have been postulated to explain the progressive neuron loss.

Over the past decade, light-based devices have received a significant amount of interest among a diverse group of medical and research clinicians. Specifically, low-level laser therapy (LLLT), because of its coherent emission of photons, has shown the greatest promise.

LLLT is a subtle instrument capable of altering cellular metabolism; therefore capable of producing a beneficial clinical effect. The basic principle of light therapy operates under photochemistry, a science dedicated to exploring the interactions between chemical and biological reactions with photons.

The first law of photochemistry states that a photoacceptor molecule must be present in order for light to influence the intra-components of a cell. Several photoacceptor molecules have been identified; however, the most important one has been found to exist within the electron transport chain of the mitochondria, Cytochrome c oxidase.

What makes this particular molecule unique is its arrangement of transition molecules; thus, enhancing its ability to possess excited electrons based on the electron configuration of the transition metals.

Cytochrome c oxidase drives electrons along the inner membrane of the mitochondria playing a pivotal role in the production of adenosine tri- phosphate (ATP) and stabilization of the intra-cellular redox state.

Subsequent to laser irradiation, Cytochrome c oxidase becomes excited, transporting electrons at a greater rate; but more importantly, moving more electrons per unit time. Overall, the excitation of Cytochrome c oxidase results in more ATP and superoxides.

The initial physical and/or chemical changes of Cytochrome c oxidase have been shown to alter the intracellular redox state. It has been proposed that the redox state of a cell regulates cellular signaling pathways that control gene expression. Modulation of the cellular redox state can activate or inhibit signaling pathways such as redox-sensitive transcription factors and/or phospholipase A2.

Two well-defined transcription factors, nuclear factor Kappa B (NF-?B) and activator protein-1 (AP-1), are regulated by the intracellular redox state. Moreover, NF-?B and AP-1 become activated following an intracellular redox shift to a more alkalized state.

Subsequent to laser irradiation, a gradual shift toward a more oxidized (alkalized) state has been observed. More importantly, the activation of redox-sensitive transcription factors and subsequent gene expression has been demonstrated. The previous transcrip- tion factors identified has being influenced by laser light represent only a pair of many transcription factors influenced by the intra-cellular redox state and laser therapy.

Based on its ability to modulate cellular metabolism and alter the transcription factors responsible for gene expression, low-level laser therapy (LLLT) has been found to alter gene expression, cellular proliferation, intra- cellular pH balance, mitochondrial membrane potential, generation of transient reactive oxygen species and calcium ion level, proton gradient, and consumption of oxygen.

Further, the proliferation of keratinocytes and fibroblasts has been reported in the literature for extremely low doses of laser irradiation. The above mentioned clinical impacts represent how the stimulation of the mitochondria via low-energy light can provoke a dynamic shift in the function of an individual cell. The mitochondrion is an important organelle that plays a vital role in persevering cell function and viability.

Recall that the underlying condition of PD is the degeneration and death of neurons responsible for the release of dopamine, an important neurotransmitter. It has been postulated that oxidative stress and mitochondrial dysfunction might attribute to the rapid degradation of the neurons.

Interestingly, laser therapy has been shown to stimulate the redox chain of the mitochondria, which is capable of controlling many parameters of cellular metabolism.  Studies have identified that the mitochondria possesses multiple mechanisms that regulate apoptosis.

Nutritionally deficient cells exposed to low-energy irradiation had greater preservation of both membranes and genetic material, and the number of apoptotic nuclei decreases compared with non-irradiated samples. It was concluded that laser therapy prevented apoptosis (Carnevalli et al. 2003).

A recent study published in 2006 (Liang et al.) showed that irradiation of rat cortical visual neurons protected them from apoptotic death induced by a potassium cyanide. Cyanide is an inhibitor of Cytochrome c oxidase; therefore, it was concluded by the authors that laser therapy was able to decrease apoptosis by stimulating Cytochrome c oxidase.

Laser therapy is a subtle instrument that influences the bioenergetics of a cell by altering the function of the mitochondria, perhaps manipulating apoptotic events of a cell.

Mitochondrial function is broad and highly important and may play a pivotal role in the degeneration of dopaminergic neurons of the substantia nigra. Laser therapy when applied could perhaps alter the bioenergics of these dopaminergic neurons, influencing its ability to appropriately secrete dopamine.

Stimulation of Cytochrome c oxidase can enhance mitochondrial function and may stabilize the intra-cellular redox state of the substantia nigra thus preventing degradation of major intracellular proteins. Although it is only proposed that laser therapy can have a beneficial impact on dopaminergic neurons, studies both clinical and histological are warranted.

 

This research was provided by Erchonia Medical Inc.

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