Parkinson's Disease and Photobiomodulation: Potential for Treatment.

Parkinson's disease is the second most common neurodegenerative disease and is increasing in incidence. The combination of motor and non-motor symptoms makes this a devastating disease for people with Parkinson's disease and their care givers. Parkinson's disease is characterised by mitochondrial dysfunction and neuronal death in the substantia nigra, a reduction in dopamine, accumulation of α-synuclein aggregates and neuroinflammation. The microbiome-gut-brain axis is also important in Parkinson's disease, involved in the spread of inflammation and aggregated α-synuclein. The mainstay of Parkinson's disease treatment is dopamine replacement therapy, which can reduce some of the motor signs. There is a need for additional treatment options to supplement available medications. Photobiomodulation (PBM) is a form of light therapy that has been shown to have multiple clinical benefits due to its enhancement of the mitochondrial electron transport chain and the subsequent increase in mitochondrial membrane potential and ATP production. PBM also modulates cellular signalling and has been shown to reduce inflammation. Clinically, PBM has been used for decades to improve wound healing, treat pain, reduce swelling and heal deep tissues. Pre-clinical experiments have indicated that PBM has the potential to improve the clinical signs of Parkinson's disease and to provide neuroprotection. This effect is seen whether the PBM is directed to the head of the animal or to other parts of the body (remotely). A small number of clinical trials has given weight to the possibility that using PBM can improve both motor and non-motor clinical signs and symptoms of Parkinson's disease and may potentially slow its progression.

Therapeutic Potential of Photobiomodulation for Chronic Kidney Disease.

Chronic kidney disease (CKD) is a growing global public health problem. The implementation of evidence-based clinical practices only defers the development of kidney failure. Death, transplantation, or dialysis are the consequences of kidney failure, resulting in a significant burden on the health system. Hence, innovative therapeutic strategies are urgently needed due to the limitations of current interventions. Photobiomodulation (PBM), a form of non-thermal light therapy, effectively mitigates mitochondrial dysfunction, reactive oxidative stress, inflammation, and gut microbiota dysbiosis, all of which are inherent in CKD. Preliminary studies suggest the benefits of PBM in multiple diseases, including CKD. Hence, this review will provide a concise summary of the underlying action mechanisms of PBM and its potential therapeutic effects on CKD. Based on the findings, PBM may represent a novel, non-invasive and non-pharmacological therapy for CKD, although more studies are necessary before PBM can be widely recommended.

Evaluation of Gender Differences in Response to Photobiomodulation Therapy, Including Laser Acupuncture: A Narrative Review and Implication to Precision Medicine.

Background: The influence of gender is significant in the manifestation and response to many diseases and in the treatment strategy. Photobiomodulation (PBM) therapy, including laser acupuncture, is an evidence-based treatment and disease prevention modality that has shown promising efficacy for a myriad of chronic and acute diseases. Anecdotal experience and limited clinical trials suggest gender differences exist in treatment outcomes to PBM therapy. There is preliminary evidence that gender may be as important as skin color in the individual response to PBM therapy. Purpose: To conduct a literature search of publications addressing the effects of gender differences in PBM therapy, including laser acupuncture, to provide a narrative review of the findings, and to explore potential mechanisms for the influence of gender. Methods: A narrative review of the literature on gender differences in PBM applications was conducted using key words relating to PBM therapy and gender. Results: A total of 13 articles were identified. Of these articles, 11 have direct experimental investigations into the response difference in gender for PBM, including laser acupuncture. A variety of cadaver, human, and experimental studies demonstrated results that gender effects were significant in PBM outcome responses, including differences in tendon structural and mechanical outcomes, and mitochondrial gene expression. One cadaver experiment showed that gender was more important than skin tone. The physiologic mechanisms directing gender differences are explored and postulated. Conclusions: The review suggests that to address the requirements of a proficient precision medicine-based strategy, it is important for PBM therapy to consider gender in its treatment plan and dosing prescription. Further research is warranted to determine the correct dose for optimal gender treatment, including gender-specific treatment plans to improve outcomes, taking into account wavelength, energy exposure, intensity, and parameters related to the deliverance of treatment to each anatomical location.

Narrative Review of Russian, Ukrainian and English-Language Publications Investigating the Effects of Photobiomodulation on Red Blood Cell Physiology.

Objective: The beneficial effects of photobiomodulation (PBM) on cellular function are well characterized, principally deriving from the absorption of red to near-infrared radiation by chromophores such as cytochrome-c-oxidase. However, the effects and underlying mechanisms of PBM on non-mitochondria containing cells, such as red blood cells (RBCs), are relatively unknown. In this review, we evaluate studies that investigated the effects of PBM on RBCs in the peripheral circulation, with particular attention on changes in the structural and functional features of RBC membrane dynamics, as well as the potential implications of PBM as an intervention for pathologies related to RBC dysfunction. Methods: A literature review was performed in concordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol, using the following databases: PubMed; Ovid (OvidMedline); Scopus; Web of Science; Google Scholar; Scholar.ru; eLIBRARY.ru; Digital Library: Dissertation; and Russian State Library. Search results included publications in Russian, Ukrainian, and English languages after 1995. Eligible articles included the effects of PBM on RBC membrane morphology and function in the peripheral circulation, used either in isolation or alongside other interventions. Results: The majority of articles indicated beneficial changes in RBC structure and function following exposure to PBM, including increased osmotic resistance, normalization of membrane permeability, decreased free radical oxidation and concentration of intermediate products of lipid peroxidation, reduced phospholipase A2 membrane activity, and normalization of the viscoelastic properties of RBCs and erythrocyte deformability index. Most trials had small patient numbers with no long-term follow-up. Conclusions: The importance of RBC membrane dysfunction as a potential marker and mechanism for RBC pathologies was highlighted. PBM has shown to have membrane protective effects. Further clinical trials are recommended to provide more evidence PBM therapy to treat RBC-related diseases, which may, at the correct dose, improve RBC stability and deformability in RBC-related pathologies.

Modifying the Microbiome as a Potential Mechanism of Photobiomodulation: A Case Report.

Objective: The objective of this case study was to elucidate the effect of photobiomodulation (PBM) on the microbiome. Background: The gut microbiome has been identified as a key component of health, with gut dysbiosis, characterized by decreased microbial diversity and an altered microbial composition, being recognized as instrumental in many diseases and disorders. Previous research has suggested that the gut microbiome can be favorably altered in animal models using PBM. Materials and methods: The participant had their microbiome tested on nine occasions, three times before any treatment, three times after radiotherapy and commencement of immunotherapy for breast cancer, and three times after PBM treatment. The PBM treatment consisted of infrared laser treatment (904 nm; 700 Hz pulse frequency, 861.3 total joules) to the abdomen three times per week for 11 weeks. Results: The microbiome of the participant showed significant changes in diversity after PBM treatment, but not after cancer therapy, with an increase in the number of known beneficial bacteria (Akkermansia, Faecalibacterium, and Roseburia) and decrease in the number of potentially pathogenic genera. Conclusions: The results suggested the possibility that PBM may alter the microbiome and thus it represents a therapeutic avenue for chronic diseases with otherwise limited treatment options.

Remote Photobiomodulation Treatment for the Clinical Signs of Parkinson's Disease: A Case Series Conducted During COVID-19.

Objective: To assess whether remote application of photobiomodulation (PBM) is effective in reducing clinical signs of Parkinson's disease (PD). Background: PD is a progressive neurodegenerative disease for which there is no cure and few treatment options. There is a strong link between the microbiome-gut-brain axis and PD. PBM in animal models can reduce the signs of PD and protect the neurons from damage when applied directly to the head or to remote parts of the body. In a clinical study, PBM has been shown to improve clinical signs of PD for up to 1 year. Methods: Seven participants were treated with PBM to the abdomen and neck three times per week for 12 weeks. Participants were assessed for mobility, balance, cognition, fine motor skill, and sense of smell on enrolment, after 12 weeks of treatment in a clinic and after 33 weeks of home treatment. Results: A number of clinical signs of PD were shown to be improved by remote PBM treatment, including mobility, cognition, dynamic balance, spiral test, and sense of smell. Improvements were individual to the participant. Some improvements were lost for certain participants during at-home treatment, which coincided with a number of enforced coronavirus disease 2019 (COVID-19) pandemic lockdown periods. Conclusions: Remote application of PBM was shown to be an effective treatment for a number of clinical signs of PD, with some being maintained for 45 weeks, despite lockdown restrictions. Improvements in clinical signs were similar to those seen with the application of remote plus transcranial PBM treatment in a previous study. Clinical Trial Registration number: U1111-1205-2035.

Improvements in clinical signs of Parkinson's disease using photobiomodulation: a prospective proof-of-concept study.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. OBJECTIVE: To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). METHODS: Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12 weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14 weeks before commencing the same treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4 weeks of treatment, after 12 weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. RESULTS: Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved (p < 0.05) with PBM treatment for 12 weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. CONCLUSIONS: PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018.

The history of light therapy in hospital physiotherapy and medicine with emphasis on Australia: Evolution into novel areas of practice.

Objective: The objective of this narrative review was to investigate the history of light therapy in hospital settings, with reference to physiotherapy and particularly in an Australian context.Types of articles and search method:a review of available literature was conducted on PubMed, Medline and Google Scholar using keywords light therapy, photobiomodulation, physiotherapy, low-level laser, heliotherapy. Physiotherapy textbooks from Sydney University Library were searched. Historical records were accessed from the San Hospital library. Interviews were conducted with the San Hospital Chief Librarian and a retired former Head Physiotherapist from Royal Prince Alfred Hospital.Summary: Historically, light treatment has been used in both medical and physiotherapy practice. From its roots in ancient Egypt, India, and Greece, through to medieval times, the modern renaissance in 'light as therapy ' was begun by Florence Nightingale who, in the 1850s, advocated the use of clean air and an abundance of sunlight to restore health. Modern light therapy (phototherapy) had a marked uptake in use in medicine in Scandinavia, America, and Australia from 1903, following the pioneering work of Niels Finsen in the late 19th century, which culminated in Dr Finsen receiving the Nobel Prize for Medicine for the treatment of tuberculosis scarring with ultraviolet (UV) light, and treatment of smallpox scarring with red light. Treatment with light, especially UVB light, has been widely applied by physiotherapists in hospitals for dermatological conditions since the 1950s, particularly in Australia, Scandinavia, USA, England and Canada. In parallel, light treatment in hospitals for hyperbilirubinemia was used for neonatal jaundice. Since the 1980s light was also used in the medical specialties of ophthalmology, dermatology, and cardiology. In more recent years in physiotherapy, light was mostly used as an adjunct to the management of orthopedic/rheumatological conditions. Since the 1990s, there has been global use of light, in the form of photobiomodulation for the management of lymphedema, including in supportive cancer care. Photobiomodulation in the form of low-level laser has been used by physiotherapists and pain doctors since the 1990s in the management of chronic pain. The use of light as therapy is exemplified by its use in the San Hospital in Sydney, where light therapy was introduced in 1903 (after Dr. John Harvey Kellogg visited Niels Finsen in Denmark) and is practiced by nurses, physiotherapists and doctors until the present day. The use of light has expanded into new and exciting practices including supportive cancer care, and treatment of depression, oral mucositis, retinopathy of prematurity, and cardiac surgery complications. Light is also being used in the treatment of neurological diseases, such as Parkinson's disease, traumatic brain injury, and multiple sclerosis. The innovative uses of light in physiotherapy treatment would not be possible without the previous experience of successful application of light treatment.Conclusion: Light therapy has had a long tradition in medicine and physiotherapy. Although it has fallen somewhat out of favour over the past decades, there has been a renewed interest using modern techniques in recent times. There has been continuous use of light as a therapy in hospitals in Australia, most particularly the San Hospital in Sydney where it has been in use for almost 120 years.

Guidelines versus evidence: what we can learn from the Australian guideline for low-level laser therapy in knee osteoarthritis? A narrative review.

This narrative review analyses the Australian Guideline (2018) for the treatment of knee osteoarthritis (KOA) developed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The Guideline recommended against the use low-level laser therapy (LLLT). Why this conclusion was reached is discussed in this review in the context of evidence provided in other systematic reviews, the latest of which was published in 2019 and which provided strong support for LLLT for knee OA. We evaluated the reference list cited for the recommendation "against" LLLT and compared this with reference lists of systematic reviews and studies published before and after the publication date of the Guideline. Eight randomised controlled trials (RCTs) of LLLT were cited in the Guideline the latest of which was published in 2012. There were seventeen additional RCTs, five of which together with one systematic review were located in the year of publication, 2018. The most recent systematic review in 2019 included 22 RCTs in its analysis. Discordance with the levels of evidence and recommendations was identified. Although GRADE methodology is said to be robust for systematically evaluating evidence and developing recommendations, many studies were not identified in the Guideline. In contrast, the latest systematic review and meta-analysis provides robust evidence for supporting the use of LLLT in knee OA. The conflict between guidelines based on opinion and evidence based on meta-analysis is highlighted. Given the totality of the evidence, we recommend that the Australian Guideline should be updated immediately to reflect a "for" recommendation.

Pre-Conditioning and Post-Operative Photobiomodulation Therapy by a Novel Light Patch System for Knee Arthroplasty: A Protocol for a Phase 1 Study.

Objective: To determine the potential efficacy and feasibility of photobiomodulation therapy (PBMT) before and after knee arthroplasty (KA) surgery. Background: Total knee replacements (total knee arthroplasty, TKA) are one of the most common and successful surgical interventions for osteoarthritis. Up to 20,000 knee replacement arthroplasties are performed in Australia annually. Although TKA aims to restore knee alignment and relieve pain in the long term, the initial post-operative period is difficult and rehabilitation is often hindered by persistent pain and swelling. A promising therapeutic approach, PBMT using a novel self-adhesive light patch system, may be feasible for reducing post-operative pain and swelling and aiding recovery. Materials and methods: This is an interventional clinical feasibility study protocol. Patients from a surgical waitlist will be invited to take part. PBMT will be applied for 30 min daily for 7 days pre-operatively using a novel light patch system (CareWear®) with both 450 nm (6.75 mW/cm2) and 640 nm (2.25 mW/cm2) microdiodes. Post-operative treatment will utilize the same device second daily for 1 week after removal of compression bandages. Results: Outcomes will be evaluated at seven time points: baseline at week 1 pre-operatively, 1 day before surgery, day 4 after surgery, weekly for a further 2 weeks, and fortnightly until 6 weeks post-hospital discharge. Outcome measures include the following: Numeric Pain Rating Scale, stair climb test, 30-sec chair stand test, timed up and go test, 40-m fast-paced walk test, modified Iowa Level of Assistance Scale, muscle strength, knee range of motion, Knee Injury and Osteoarthritis Outcome Score, and Lower Limb Functional Index. Conclusions: This study will provide an assessment of feasibility of using PBMT applied using a novel light patch system for management of pain symptoms and swelling, and aiding recovery of patients undergoing TKA. The results of this feasibility study will contribute to planning of the design and methods of a large clinical trial.

"Photobiomics": Can Light, Including Photobiomodulation, Alter the Microbiome?

Objective: The objective of this review is to consider the dual effects of microbiome and photobiomodulation (PBM) on human health and to suggest a relationship between these two as a novel mechanism. Background: PBM describes the use of low levels of visible or near-infrared (NIR) light to heal and stimulate tissue, and to relieve pain and inflammation. In recent years, PBM has been applied to the head as an investigative approach to treat diverse brain diseases such as stroke, traumatic brain injury (TBI), Alzheimer's and Parkinson's diseases, and psychiatric disorders. Also, in recent years, increasing attention has been paid to the total microbial population that colonizes the human body, chiefly in the gut and the mouth, called the microbiome. It is known that the composition and health of the gut microbiome affects many diseases related to metabolism, obesity, cardiovascular disorders, autoimmunity, and even brain disorders. Materials and methods: A literature search was conducted for published reports on the effect of light on the microbiome. Results: Recent work by our research group has demonstrated that PBM (red and NIR light) delivered to the abdomen in mice, can alter the gut microbiome in a potentially beneficial way. This has also now been demonstrated in human subjects. Conclusions: In consideration of the known effects of PBM on metabolomics, and the now demonstrated effects of PBM on the microbiome, as well as other effects of light on the microbiome, including modulating circadian rhythms, the present perspective introduces a new term "photobiomics" and looks forward to the application of PBM to influence the microbiome in humans. Some mechanisms by which this phenomenon might occur are considered.

Photobiomodulation of the microbiome: implications for metabolic and inflammatory diseases.

The human microbiome is intimately associated with human health, with a role in obesity, metabolic diseases such as type 2 diabetes, and divergent diseases such as cardiovascular and neurodegenerative diseases. The microbiome can be changed by diet, probiotics, and faecal transplants, which has flow-on effects to health outcomes. Photobiomodulation has a therapeutic effect on inflammation and neurological disorders (amongst others) and has been reported to influence metabolic disorders and obesity. The aim of this study was to examine the possibility that PBM could influence the microbiome of mice. Mice had their abdomen irradiated with red (660 nm) or infrared (808 nm) low-level laser, either as single or multiple doses, over a 2-week period. Genomic DNA extracted from faecal pellets was pyrosequenced for the 16S rRNA gene. There was a significant (p < 0.05) difference in microbial diversity between PBM- and sham-treated mice. One genus of bacterium (Allobaculum) significantly increased (p < 0.001) after infrared (but not red light) PBM by day 14. Despite being a preliminary trial with small experimental numbers, we have demonstrated for the first time that PBM can alter microbiome diversity in healthy mice and increase numbers of Allobaculum, a bacterium associated with a healthy microbiome. This change is most probably a result of PBMt affecting the host, which in turn influenced the microbiome. If this is confirmed in humans, the possibility exists for PBMt to be used as an adjunct therapy in treatment of obesity and other lifestyle-related disorders, as well as cardiovascular and neurodegenerative diseases. The clinical implications of altering the microbiome using PBM warrants further investigation.

A Role for Photobiomodulation in the Prevention of Myocardial Ischemic Reperfusion Injury: A Systematic Review and Potential Molecular Mechanisms.

Myocardial ischemia reperfusion injury is a negative pathophysiological event that may result in cardiac cell apoptosis and is a result of coronary revascularization and cardiac intervention procedures. The resulting loss of cardiomyocyte cells and the formation of scar tissue, leads to impaired heart function, a major prognostic determinant of long-term cardiac outcomes. Photobiomodulation is a novel cardiac intervention that has displayed therapeutic effects in reducing myocardial ischemia reperfusion related myocardial injury in animal models. A growing body of evidence supporting the use of photobiomodulation in myocardial infarct models has implicated multiple molecular interactions. A systematic review was conducted to identify the strength of the evidence for the therapeutic effect of photobiomodulation and to summarise the current evidence as to its mechanisms. Photobiomodulation in animal models showed consistently positive effects over a range of wavelengths and application parameters, with reductions in total infarct size (up to 76%), decreases in inflammation and scarring, and increases in tissue repair. Multiple molecular pathways were identified, including modulation of inflammatory cytokines, signalling molecules, transcription factors, enzymes and antioxidants. Current evidence regarding the use of photobiomodulation in acute and planned cardiac intervention is at an early stage but is sufficient to inform on clinical trials.