Showing posts with label Laser. Show all posts
Showing posts with label Laser. Show all posts

Thursday, 4 July 2019

Home/Clinic based Photobiomodulation/Laser Therapy in Autism - acting on Light Sensitive Ion Channels, Mitochondria, Lymph Nodes and more

Photobiomodulation underlying mechanisms at the cellular and molecular levels. Light at 600–850 nm is absorbed by the mitochondrial electron transfer chain and leads to upregulation of the neuronal respiratory capacity. The near-infrared light at range of 900– 1100 nm is absorbed by structured water clusters formed in or on a heat/light-gated ion channels. An increase in vibrational energy of water cluster leads to perturb the protein structure and opening the channel which ultimately allows modulation of intracellular Ca2+ levels. The absorption of green light by neuronal opsin photoreceptors (OPN2-5) activates transient receptor potential channels which causes nonselective permeabilization to Ca2+ , Na+ , and Mg2+ . The cryptochromes (a class of flavoprotein blue-light signaling receptors) absorb blue light and seems to activate the transducing cellular signals via part of the optic nerve to the suprachiasmatic nucleus in the brain, which is important in regulation of the circadian clock

Today we return to the idea of using low power lasers to treat autism.  This follows on from the original post that reviewed a credible clinical trial that compared laser therapy with a sham red light therapy.  My conclusion was either the researchers cheated, or it really did work.   It is a pity, but experience shows us that cheating does occur in published research. I also pondered whether a cheaper LED device could give the same benefit of an expensive laser.

Low Level Laser Therapy (LLLT) for Autism – seems to work in Havana

Our reader RD has been busy at home applying the research, first using LEDs to no avail, before moving on to an expensive laser device, which does provide a benefit.  Today we dig a little deeper about what might be going on inside the brains of people treated with such devices. Click below to read RD's extensive comments and interesting links.

Some autism therapies involving the use of expensive gadgets do set alarm bells ringing, but the more you look into Photobio-modulation, which is the new name of Low Level Laser Therapy (LLLT), the more credible it becomes.  There has been a great deal of recent research regarding other neurological conditions, autism only rarely gets a mention. The same therapy has been used on different parts of the body for several decades in Russia and some other countries. Where we live physiotherapists use Photobiomodulation/LLLT to treat numerous types of ache and pain.

It is still early days for Photobiomodulation and the brain. A lot depends on which parts of the brain you want to target; there are even plans for using the mouth, nose and ears as entry points to reach different parts of the brain.

Heat/light sensitive ion channels

Many human diseases are associated with ion channel dysfunctions (channelopathies).  Many people with autism have either genetic or acquired channelopathies of one kind or another.

Today our focus on light introduces us to a class of ion channels activated by heat and/or light.

We should immediately recall the so called “fever effect” in autism where in some people a rise in body temperature improved their autism, sometimes dramatically. The fever effect was replicated by one US researcher having people sit in a hot tub.


 Five control subjects without a history of fever completed the hyperthermia condition at 102 °F, and demonstrated the safety and feasibility of the study. Ten subjects with ASD and a history of fever response were enrolled and completed the hyperthermia condition (102 °F) and control condition (98 °F) at the aquatic therapy pool. Improvement in social cognition and repetitive/restrictive behaviors were observed at the hyperthermia condition (102 °F) on parent (SRS, RBS-R) and rater (CGI-I) assessments. Pupillometry biomarker and gene expression can be correlated with clinical improvement. Side effects were minimal, and were the same as those observed in a hot tub/sauna (redness, nausea).


We demonstrated improvement of socialization and repetitive and restricted behaviors at the hyperthermia condition (102 °F), and that we could reliably and safely increase children’s temperatures into the fever range (mean max temperature of 101.7 °F). This temperature increase was observed to cause significant and convergent improvement on clinician ratings (CGI-I) and parent ratings (SRS, RBS-R), both of which were kept blinded to the temperature of the pool. Interestingly, each child’s fever response history was correlated with the improvements observed at the elevated temperature. Those with a history of marked fever response had the most observable behavior changes. Behavior changes observed for each child were similar to those observed by parents during febrile episodes, including increased cooperation, communication and social reciprocity and decreased hyperactivity and inappropriate vocalizations. Although multiple rationales have been posited, this is the first study looking at the direct effect of temperature on ASD symptomatology.

TRPV1 and Autism

There has been a link suggested between TRPV1 and autism.  SHANK3 is a single gene type of autism, often used to study autism.

In control mice, SHANK3 tethers a protein called TRPV1 to the surface of sensory neurons, where it detects heat and chemical signals. Those signals activate TRPV1, causing calcium ions to flood into the cell, leading to a painful sensation.
Neurons from control mice show a robust influx of calcium ions in response to capsaicin, the chemical that gives chili peppers their heat. But the chemical triggers significantly less calcium flow into neurons from SHANK3 mice.
The study stokes curiosity about the connection between autism and TRPV1. This protein aids heart and lung function, and has been linked to addiction, anxiety and depression, says Camilla Bellone, assistant professor of neuroscience at the University of Geneva in Switzerland, who was not involved in the study. “It would be really interesting to see if TRPV1 dysfunction could explain other [features] associated with autism,” she says.

Pain, Rett Syndrome, MECP2 and TRPV1

It appears to be not just SHANK3 autism that has a TRPV1 connection, so does the all-female Rett Sydrome. Here the connection relates to unusual pain sensitivity in Rett Sydrome. Many people with autism have an unusual relationship with pain.

Although TRPV1 was expressed in MeCP2-positive TG neurons innervating the tongue in both wild-type and Mecp2+/- mice, a significantly smaller number of TRPV1-positive neurons were observed in the tongues of heterozygotes compared to wild-types. Together, these data suggest that the hypoalgesia observed in this mouse model is induced by the inhibition of TRPV1 expression, and this expression is dependent in part on MeCP2 signaling.
These findings suggest that tongue heat sensitivity and inflammatory hyperalgesia are dependent on TRPV1 expression in TG neurons that innervate the tongue and that this expression is regulated by MeCP2 signaling, supporting a role for MeCP2 in pain modulation. Hypoalgesia is a potentially dangerous condition that may result in more severe tissue damage from burns or other physical trauma due to a blunted pain withdrawal reflex.  Understanding how MeCP2 modulates pain might lead to therapies that improve the pain sensitivity in Rett syndrome patients, as well as treatments that might help to reduce neuropathic pain associated with other genetic or acquired conditions.

TRPV Channels in Mast Cells as a Target for Low-Level-Laser Therapy

Low-level laser irradiation in the visible as well as infrared range is applied to skin for treatment of various diseases. Here we summarize and discuss effects of laser irradiation on mast cells that leads to degranulation of the cells. This process may contribute to initial steps in the final medical effects. We suggest that activation of TRPV channels in the mast cells forms a basis for the underlying mechanisms and that released ATP and histamine may be putative mediators for therapeutic effects.

Modulation of TRPV channel gating by light-switched ligand. Putative modulation of an azo-chromophore between cis- and trans-form by light leading to activation of TRPV channel opening. As an example TRPV activation by the cis-form is cartooned.

We have shown in this review that laser irradiation in the visible and IR as well as UV range can modulate the function and expression of TRPV ion channels, and in particular TRPV1, TRPV2, and TRPV4. This may form the basis for effect of LLLT. As Ca2+-permeable ion channels, their activation may contribute to the laser-induced increase in intracellular Ca2+ that triggers degranulation and endocytotic release of ATP. Such light-induced mechanism may contribute to the basis of the medical effects of LLLT. This hypothesis still needs confirmation in animal tests and clinical trials.

Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy

Photobiomodulation (PBM) also known as low-level laser (or light) therapy (LLLT), has been known for almost 50 years but still has not gained widespread acceptance, largely due to uncertainty about the molecular, cellular, and tissular mechanisms of action. However, in recent years, much knowledge has been gained in this area, which will be summarized in this review. One of the most important chromophores is cytochrome c oxidase (unit IV in the mitochondrial respiratory chain), which contains both heme and copper centers and absorbs light into the near-infra-red region. The leading hypothesis is that the photons dissociate inhibitory nitric oxide from the enzyme, leading to an increase in electron transport, mitochondrial membrane potential and ATP production. Another hypothesis concerns light-sensitive ion channels that can be activated allowing calcium to enter the cell. After the initial photon absorption events, numerous signaling pathways are activated via reactive oxygen species, cyclic AMP, NO and Ca2+, leading to activation of transcription factors. These transcription factors can lead to increased expression of genes related to protein synthesis, cell migration and proliferation, anti-inflammatory signaling, anti-apoptotic proteins, antioxidant enzymes. Stem cells and progenitor cells appear to be particularly susceptible to LLLT.


Light sensitive ion channels

The most well-known ion channels that can be directly gated by light are the channelrhodopsins (ChRs), which are seven-transmembrane-domain proteins that can be naturally found in algae providing them with light perception. Once activated by light, these cation channels open and depolarize the membrane. They are currently being applied in neuroscientific research in the new discipline of optogenetics [35].
However, members of another broad group of ion-channels are now known to be light sensitive [36]. These channels are called "transient receptor potential" (TRP) channels as they were first discovered in a Drosophila mutant [36] and are responsible for vision in insects. There are now at least 50 different known TRP isoforms distributed amongst seven subfamilies [37], namely the TRPC (‘Canonical’) subfamily, the TRPV (‘Vanilloid’), the TRPM (‘Melastatin’), the TRPP (‘Polycystin’), the TRPML (‘Mucolipin’), the TRPA (‘Ankyrin’) and the TRPN (‘NOMPC’) subfamilies (see Figure 2). A wide range of stimuli modulate the activity of different TRP such as light, heat, cold, sound, noxious chemicals, mechanical forces, hormones, neurotransmitters, spices, and voltage. TRP are calcium channels modulated by phosphoinositides [38].


Low levels of red/NIR light can interact with cells, leading to changes at the molecular, cellular and tissue levels. Each tissue, however, can respond to this light-interaction differently, although it is well known that the photons, especially in the red or NIR, are predominantly absorbed in the mitochondria [132]. Therefore, it is likely that even the diverse results observed with PBM share the basic mechanism of action. What happens after the photon absorption is yet to be fully described, since many signaling pathways seem to be activated. It seems that the effects of PBM are due to an increase in the oxidative metabolism in the mitochondria [133]. Different outcomes can occur depending on the cell type, i.e. cancer cells that tend to proliferate when PBM is delivered [88]. In this review we have not discussed the response of cells and tissues to wavelengths longer than NIR, namely far IR radiation (FIR) (3 µm to 50 µm). At these wavelengths water molecules are the only credible chromophores, and the concept of structured water layers that build up on biological lipid bilayer membranes has been introduced to explain the selective absorption [134]. Nevertheless FIR therapy has significant medical benefits that are somewhat similar to those of PBM [135], and it is possible that activation of light/heat sensitive ion channels could be the missing connection between the two approaches.
As we have shown, PBM can regulate many biological processes, such as cell viability, cell proliferation and apoptosis, and these processes are dependent on molecules like protein kinase c (PKC), protein kinase B (Akt/PKB), Src tyrosine kinases and interleukin-8/1a (IL-8/1a). The effects of light on cell proliferation can be stimulatory at low fluences (which is useful in wound healing, for instance), but could be inhibitory at higher light doses (which could be useful in certain types of scar formation such as hypertrophic scars and keloids) [131].
The applications of PBM are broad. Four clinical targets, however, are the most common: shining light on injured sites to promote healing, remodeling and/or to reduce inflammation; on nerves to induce analgesia; on lymph nodes in order to reduce edema and inflammation; and on trigger points (a single one of as many as 15 points) to promote muscle relaxation and to reduce tenderness. Since it is non invasive, PBM is very useful for patients who are needle phobic or for those who cannot tolerate therapies with non-steroidal anti-inflammatory drugs [83].
The positive outcomes depend on the parameters used on the treatment. The anti-inflammatory effect of light in low intensity was reported on patients with arthritis, acrodermatitis continua, sensitive and erythematous skin, for instance [136]. With the same basic mechanism of action, which is the light absorption by mitochondrial chromophores, mainly Cox, the consequences of PBM are various, depending on the parameters used, on the signaling pathways that are activated and on the treated tissue. In order to apply PBM in clinical procedures, the clinicians should be aware of the correct parameters and the consequences for each tissue to be treated. More studies have to be performed in order to fill the gaps that still linger in the basic mechanisms underlying LLLT and PBM.

Photobiomodulation improves the frontal cognitive function of older adults.


The frontal lobe hypothesis of age-related cognitive decline suggests that the deterioration of the prefrontal cortical regions that occurs with aging leads to executive function deficits. Photobiomodulation (PBM) is a newly developed, noninvasive technique for enhancing brain function, which has shown promising effects on cognitive function in both animals and humans. This randomized, sham-controlled study sought to examine the effects of PBM on the frontal brain function of older adults.


Thirty older adults without a neuropsychiatric history performed cognitive tests of frontal function (ie, the Eriksen flanker and category fluency tests) before and after a single 7.5-minute session of real or sham PBM. The PBM device consisted of three separate light-emitting diode cluster heads (633 and 870 nm), which were applied to both sides of the forehead and posterior midline, and delivered a total energy of 1349 J.


Significant group (experimental, control) × time (pre-PBM, post-PBM) interactions were found for the flanker and category fluency test scores. Specifically, only the older adults who received real PBM exhibited significant improvements in their action selection, inhibition ability, and mental flexibility after vs before PBM.


Our findings support that PBM may enhance the frontal brain functions of older adults in a safe and cost-effective manner.

Brain Photobiomodulation Therapy: a Narrative Review.

Brain photobiomodulation (PBM) therapy using red to near-infrared (NIR) light is an innovative treatment for a wide range of neurological and psychological conditions. Red/NIR light is able to stimulate complex IV of the mitochondrial respiratory chain (cytochrome c oxidase) and increase ATP synthesis. Moreover, light absorption by ion channels results in release of Ca2+ and leads to activation of transcription factors and gene expression. Brain PBM therapy enhances the metabolic capacity of neurons and stimulates anti-inflammatory, anti-apoptotic, and antioxidant responses, as well as neurogenesis and synaptogenesis. Its therapeutic role in disorders such as dementia and Parkinson's disease, as well as to treat stroke, brain trauma, and depression has gained increasing interest. In the transcranial PBM approach, delivering a sufficient dose to achieve optimal stimulation is challenging due to exponential attenuation of light penetration in tissue. Alternative approaches such as intracranial and intranasal light delivery methods have been suggested to overcome this limitation. This article reviews the state-of-the-art preclinical and clinical evidence regarding the efficacy of brain PBM therapy.

Because neural tissues contain large amounts of mitochondrial CCO, application of red to NIR lights (600–850) for brain PBM therapy is highly attractive. The main problem so far has been getting enough light into the brain to accomplish the beneficial effects. In recent years, irradiation in the wavelength range between 980 and 1100 nm has been growing rapidly, and its different mechanisms of action including stimulation of ion channels and water molecules suggest it might even be combined with red/NIR. Improving cerebral metabolic function, stimulating neurogenesis and synaptogenesis, regulating neurotransmitters, and providing neuroprotection via anti-inflammatory and antioxidant biological signaling are the most important effects of brain PBM therapy (Fig. 4). The overall results from extensive preclinical and clinical studies in the brain PBM field suggest that modest levels of red and NIR light show biostimulatory effects without any thermal damage, and could improve neurobehavioral deficits associated with many brain disorders. Nevertheless, it is still not completely clear whether chronic repetition of brain PBM will be necessary for sustained clinical benefit, especially in psychological and neurodegenerative disorders. Owing to the beneficial impacts of brain PBM therapy in depression and anxiety, new trials for other psychiatric disorders such as schizophrenia autism, , bipolar, attention-deficit hyperactivity, and obsessive–compulsive disorders might well emerge in the future. Development of new techniques for effective light delivery to deeper structures of the brain is crucial, because of involvement of the limbic system and midbrain abnormalities seen in some brain disorders. In this respect, intracranial and intranasal irradiation methods, as well as the oral cavity route, even via the ear canal could be options. Although therapeutic influences of intracranial PBM therapy has been focused on PD researches, it is postulated that developing this technique also potentially effective for those conditions that are associated with limbic system dysfunctions such as anhedonia, anxiety, as well as impaired emotional processing. Preliminary evidence of benefit has been obtained in autism spectrum disorders. There is an epidemic of AD that is expected to hit the Western world as the overall population ages, and there has been a noticeable lack of any effective pharmacological therapies that have been approved for AD. Although the evidence for the effectiveness of PBM in the treatment of AD is still very preliminary, it is possible that PBM will play an even larger role in society in years to come if clinical trials now being conducted are successful. The authors conclude that clinic or home-based PBM therapy using laser or LED devices will become one of the most promising strategies for neurorehabilitation in upcoming years


Our reader RD is well ahead of the curve with his PBM/LLLT investigation. I do not see this kind of therapy being adopted by mainstream Western medicine, even if it did work.  It has been used in other countries for many decades by medical doctors, for all kinds of conditions, but that fact does not cut it with most Western doctors.  There are  practitioners of PBM/LLLT in Western countries, but they tend to be on the fringes of medicine, which puts PBM/LLLT clearly in the crank therapy category for most qualified Western doctors.

On the basis that we should keep an open mind about all kinds of therapies, we should consider PBM further. It is apparently safe at the power levels used. It may look a little strange, but it is non-invasive and the therapy does not take long. A single device could easily be used to treat many people, so the high price should not remain a barrier.

I was very surprised to hear that a local speech therapy company is now offering “neurofeedback therapy” using an expensive machine they have bought. I was very suspicious of a recent study carried out in Florida that was put forward to support this therapy using a commercial device, since of the 42 children in the group that had the actual therapy only 17 completed the 12 week trial and came back for the evaluation.  The trial included a similar sized group who had a sham therapy.  The likelihood of completing the trial was the same in both groups, which also looks odd.

Of the 83 subjects that completed the evaluation at the enrollment time, 34 returned for the POST evaluation after the 12 weeks of home based therapy.

If the results were so good, why did the majority of parents walk away during the trial? I was going to suggest to the speech therapist that perhaps those few thousands of euros/dollars might have been better spent on a laser, or perhaps the lottery.

For me, one big question about the laser is about how the device is used. Depending on what you believe the mode of action to be, you would have to use it in completely different ways.

If the benefit relates to improved mitochondrial function, you should really be able to measure this benefit using a PET scan that measures glucose uptake to each part of the brain. This was the method proposed by Polish researchers to show how some people benefit from a ketogenic diet to improve power/ATP output from different parts of the brain.

You would hope other researchers would try and replicate the benefit in autism, but the first group have already patented the laser idea.

Hopefully our reader RD will perfect this therapy and we await his feedback.

I did recently write about the recently discovered lymphatic system within the brain. One proposed benefit of PBM/LLLT is improved drainage of lymph. I thought that was interesting; if it was actually true then this therapy could potentially be used to prevent the onset of Alzheimer’s. We saw in that post that faulty lymph drainage may allow the accumulation of waste products (plaques etc) in aging brains and then Alzheimer's develops. Targeting the relevant lymph node with PBM/LLLT might be an alternative to the drug therapy currently being developed.

I am told that lymphatic drainage is currently "the big thing" in autism in the US, alongside anything to do with CBD (cannabis). Hopefully in the fb world of autism they have noted that in MS the problem with the brain's lymphatic system was not drainage, but the ingress of inflammatory messengers from the body into the brain, suggesting the opposite therapy.

Thursday, 13 December 2018

Low Level Laser Therapy (LLLT) for Autism – seems to work in Havana

Today’s post is all about one of the potential medical, but non-drug, interventions for autism. The others tend to involve electrical/magnetic stimulation of one kind or another.
Low level laser therapy (LLLT) was developed more than fifty years ago in Russia. Today in Western countries LLLT is often regarded as alternative medicine or just quackery.  There are some FDA approved devices.  In Russia and some East European countries LLLT is part of mainstream medicine.
Two people forwarded me a recent study that was carried out in Havana by a team from Cuba and Israel.
There are only 11 million Cubans, but there are a lot of Cuban doctors.  They have developed interesting drugs, some related to cancer, that are now being taken up by Western medicine.  Cuba actually leases out doctors to work in more than 50 developing countries around the world.
The results of the study are indeed interesting and there is a long list of possible mechanisms that may be involved.
The question we are left with is can you achieve a similar result with cheap LEDs (light emitting diodes), or do you need a genuine laser (that confusingly use a different kind of diode).  I do not know the answer, but there is definitely a difference.  

Let’s start with the background to LLLT

 In Russia (formerly USSR) study of biomodulation action (BMA) mechanisms of low-intensity laser irradiation (LILI) began in 1964, immediately after the development of lasers. During the period from 1965 to 1972 several dozens of scientific conferences were held, hundreds of studies were published. Generally, secondary mechanisms and results of LILI effect on patients with various diseases were studied. This data was immediately implemented into practical medicine in the fields of oncology, surgery, dermatology and dentistry, and since 1974 low level laser therapy (LLLT) is included in the standard of state medical care. For 50 years no less than 1000 books were published (monographs, collections, methodical and clinical materials), thousands of researches were carried out. Primary mechanism and patterns of interaction of LILI with acceptors within cells can be represented in the following order: absorption of photon’s energy – emergence of a local temperature gradient – release of Ca2+ from intracellular stores – stimulating Ca2+–dependent processes. Understanding of this process allowed the explanation of all known secondary effects, optimized methods and extremely increased effectiveness of LLLT. Owing to the knowledge of BMA mechanisms of LILI, numerous associated and combined LLLT techniques were developed and are widely used nowadays: locally, on the projection of internal organs, laser acupuncture, reflexology, intracavitary, transdermal and intravenous laser blood illumination, magnetic-laser therapy, laser phoresis, laser-vacuum massage, biomodulation, etc. About 400 000 laser therapeutic devices are used in Russian practical healthcare. Unique, having no analogues in the world devices, are produced – red pulsed laser diodes (wavelength 635 nm, power 5-40 W, pulse duration 100 ns, frequency 10 000 Hz) are designed specially for effective laser therapy. 

About 400 000 laser therapeutic devices are used in Russian practical healthcare; about half of them are used in professional medicine (clinics), and half of them – at patients’ home for independent use. Around the world only lasers designed for other purposes (technical) are used, which are not always effective in medicine. The peculiarity of Russian laser therapeutic apparatus is the development and production of special lasers, designed specifically for therapy. For example, unique, having no analogues in the world, devices are produced - red pulsed laser diodes (wavelength 635 nm, power 5-40 W, pulse duration 100 ns, frequency 10 000 Hz) are designed specially for effective laser therapy.
Laser therapy is widely used in almost all medicine fields: obstetrics and gynecology, gastroenterology, cardiology, dermatology and cosmetology, neurology, oncology, otolaryngology, pediatrics, pulmonology, dentistry, traumatology and orthopedics (diseases of musculoskeletal system), urology and andrology, phthisiology, etc. 

Cheap LEDS vs Expensive Lasers? This paper says you cannot cut corners.

The question of lasers' exclusivity, as well as the degree of influence of special properties of low-intensity laser illumination (LILI), such as coherence, polarity and monochromaticity, on the effectiveness of low level laser therapy (LLLT) continues to cause arguments.
The study analyzes publications from 1973 to 2016, in which laser and conventional light sources are compared, and the following conclusions are drawn. First, there are a lot of publications with incorrect comparison or unfounded statements. Secondly, other sources of light are often meant by LILI without any justification. Thirdly, all studies, in which the comparison is carried out correctly and close parameters of the impact and the model are used, have a firm conclusion that laser light is much more effective. Fourthly, it is uniquely identified that the most important parameter that determines the efficiency of lasers is monochromaticity, i.e., a much narrower spectral width than for all other light sources.

Only laser light sources can be used for LLLT! 

Here is the Cuban study on autism using lasers:-

The study examined the efficacy of low-level laser therapy, a form of photobiomodulation, for the treatment of irritability associated with autistic spectrum disorder in children and adolescents aged 5–17 years. Twenty-one of the 40 participants received eight 5-min procedures administered to the base of the skull and temporal areas across a 4-week period (test, i.e., active treatment participants). All the participants were evaluated with the Aberrant Behavior Checklist (ABC), with the global scale and five subscales (irritability/agitation, lethargy/social withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech), and the Clinical Global Impressions (CGI) Scale including a severity of-illness scale (CGI-S) and a global improvement/change scale (CGI-C). The evaluation took place at baseline, week 2 (interim), week 4 (endpoint), and week 8 (postprocedure) of the study. The adjusted mean difference in the baseline to study endpoint change in the ABC irritability subscale score between test and placebo participants was _15.17 in favor of the test procedure group. ANCOVA analysis found this difference to be statistically significant (F ¼ 99.34, p < 0.0001) compared to the baseline ABC irritability subscale score. The study found that low-level laser therapy could be an effective tool for reducing irritability and other symptoms and behaviors associated with the autistic spectrum disorder in children and adolescents, with positive changes maintained and augmented over time. 

A pulsed laser of 635 nm with a power output of 15 mW and a red 635 nm LED were used as treatment and placebo, respectively.

 A significant literature exists on the ability of low-level light therapy (LLLT) to penetrate the skull. Low-energy light passes the skull and a therapeutic effect likely exists. LLLT systems employ the so-called quantum optically induced transparency effect. This effect controls optical properties of dense media enhancing transparency contrast by a factor of five. Therefore, the skull, spine, or joints can be penetrated even with moderate intensity light reaching deep layers in muscles, connective tissue, and even bone, enabling transcranial effects of LLLT.
LLLT achieves a therapeutic effect by employing non-ionizing light, including lasers, light-emitting diodes, or broadband light in the visible red (600–700 nm) and near-infrared (780–1100 nm) spectra. LLLT is a nonthermal process occurring when a chromophore is exposed to a suitable wavelength of light. Chromophores are responsible for the color associated with biological compounds such as hemoglobin and cytochromes. With chromophore absorption of a photon of light, an electron transits to an excited state, with a physiologic effect occurring when photons dissociate the inhibitory signaling molecule nitric oxide (NO) from cytochrome-C-oxidase, increasing the electron transport, mitochondrial membrane potentials, and production of mitochondrial products such as ATP and NADH. Other effects include the production of reactive oxygen species (ROS) which activate transcription factors, leading to the cellular proliferation and migration.

Based on these complex characteristics, LLLT possesses physiologically modifying properties associated with light characteristics such as wavelength and irradiance, varied by exposure parameters, such as energy density, irradiation duration, and treatment frequency. On the basis of the above, we investigated behavioral and cognitive changes in ASD as a consequence of the delivery of red LLLT.

2.4 Procedure
All the 40 participants completed the course according to the protocol. Twenty-one of them were randomized to the test (active treatment) procedure group, and 19 were randomized to the placebo procedure group. Participants received eight 5-min laser light applications to the base of the skull and temporal areas with the Erchonia® EAL Laser (active or sham) across a 4-week period: two applications per week, 3–4 days apart at the investigator’s test site.A pulsed laser of 635 nm with a power output of 15 mW and a red 635 nm LED were used as treatment and placebo, respectively. Participants were required to maintain their regular medication schedule and treatment regimens, as reported at the baseline evaluation, to treat symptoms related to autistic disorder throughout the study time. All of them complied with this requirement.  

Twenty out of the 21 active treatment participants showed some degree of improvement in autism-related symptoms at endpoint relative to baseline. The majority (13) received ratings of “much improved”. No placebo group participant demonstrated improvement in symptoms at endpoint relative to baseline. The majority (17) demonstrated “no change”, and the remaining 2 placebo participants rated “minimally worse”. We found that the ABC global and five subscale scores decreased progressively and significantly from baseline across each of the three successive evaluation points; the decrease progressed over time, including a 4-week followup during which no further LLLT occurred. Conversely, the placebo group demonstrated no significant change across the study duration, demonstrating the effectiveness of LLLT in reducing ASD-associated symptoms.

Either the researchers have cheated, which has been known to happen, or Low Level Laser Therapy (LLLT) is indeed a worthwhile therapy for much autism.  The question of safety should be carefully considered.

Judging by the drugs the participants had been taking, they were not kids with trivial autism.

According to the current FDA standards, an FDA cleared LLLT device (also called a cold laser) can be sold for 3 main issues: 
·        Pain Control

·        Inflammation Reduction

·        Increased Blood Flow  

The cheapest FDA approved laser device that would be vaguely equivalent to the device used in the trial in Cuba costs $2500 in the US.
Hopefully, one day someone will compare the effect on subjects with autism of cheap LED devices versus true laser devices.

This press release was highlighted by our reader RD:-

Erchonia Submits Data to US FDA to Support Low-Level Laser 510(k) Market Clearance for Autism
Quadruple-Blind laser study proves success in treating Autism in children and adolescents.
“The results are so strong, nobody can argue them.”

MELBOURNE, Fla. (PRWEB)September 05, 2018
Erchonia, the World Leader in Low Level Laser technology, announces today that they have submitted data to the US FDA to support a 510(k) market clearance for Autism.
The clinical trial was a quadruple-blind (Participant, Care Provider, Investigator and Outcome Assessor), randomized, placebo-controlled, and crossover clinical trial. The study was designed to treat autistic children with the 640nm Erchonia Spectrum Laser as the active device or a 640nm LED or light emitting diode as a placebo device, which had the same power output. FDA input was obtained prior to clinical trial and implemented into the protocol.
Both test and placebo patients were treated twice a week for 4 weeks. Post-treatment follow-up on both sets of patients was performed after 4 weeks, 8 weeks, and 6 months. At the end of 6 months, patients from the LED placebo group were crossed over and then given Erchonia’s Spectrum Laser treatment protocol. The results were documented and submitted to the US FDA for a 510(k) market clearance De Novo Application.
The inclusion criteria consisted of autistic children between the ages of 5 to 17 years old, and progress was measured by using the ABC or Aberrant Behavior Checklist as the primary diagnosis. The ABC 58-point symptom checklist was used to assess and classify behaviors of irritability and agitation; lethargy and social withdrawal, stereotypic behavior, hyperactivity and noncompliance, and inappropriate speech in children with developmental disorders. The ABC tests were performed at baseline, 2 weeks, and 4 weeks during the treatments phase, and 4 weeks, 8 weeks, and 6 months post-treatment in both the treated and placebo groups.
“This is a well-designed trial that shows evidence supporting the use of Low Level Laser Therapy in children and adolescents with autism,” said Dr. Morales-Quezada, Associate Research Director at Spaulding-Labushagne Neuromodulation Center. “Moreover, the technique proved to be safe and well tolerated by the study participants. The active intervention showed to be more effective than the placebo (sham) device in treating symptoms of autistic disorder, and this statistically significant treatment effect was observed for all clinical outcomes, by the end of the intervention period and after the 6 months follow-up. This evidence offers a new treatment option to be considered for children and adolescents with autism.”
Calixto Machado, MD, PhD, FAAN, President of the Cuban Society of the Clinical Neurophysiology Institute of Neurology and Neurosurgery agreed, “Results are so strong, nobody can argue them.”
Steven Shanks, President of Erchonia stated, “This study from a scientific perspective is one of the most stringent ways to perform a clinical trial. The original placebo patients have now acted as their own control group. The LED that was used as a placebo showed no results even though we used the same wavelength and power output.”
The Erchonia Spectrum Laser implemented in this clinical trial was a prototype laser and is not currently sold. While waiting for the 510(k) market clearance, Erchonia will start the development process for the new Erchonia Spectrum Laser.
Erchonia would like to thank Calixto Machado, MD, PhD, FAAN, Mauricio Chinchilla, MD, Yanin Ferrer, MD, and the University of Havana for their dedication to research and helping Erchonia with its latest achievement.
About Erchonia. Erchonia created the low-level laser category in January 2002 when the FDA granted Erchonia the very 1st 510(k) market clearance for any low-level laser. This new study further sets Erchonia apart from its competitors based on their commitment to research and numerous 510(k) market clearances obtained through blind and controlled clinical trials.