#Industry News
Weber Medical presents: Transcranial Photobiomodulation to treat Autism Spectrum Disorder
Results of the latest studies and an exploration of potential mechanisms of action
Note: This article was originally posted on the substack "light and equanimity", please find the link below.
Bottom line
tPBM is currently emerging as a potentially ideal treatment option for patients who have Autism Spectrum Disorder. Three small studies on both children and adults showed significant improvement in various symptoms that typically characterize the disease, such as problems in social interaction / communication and restricted / repetitive behaviors. The therapy was also highlighted as safe and practical in its application, including home use. Furthermore, the stress of caregivers can be reduced. Particularly the lack of effective holistic treatment options provides strong reasons that tPBM should be used for patients with ASD. However, there is still a clear need for more, especially more extensive clinical trials, before official recommendations can be made.
Introduction: Brief facts about Autism
In my last post, I summarized the most important mechanisms of transcranial photobiomodulation therapy and described how the treatment can be applied to treat dementia and Alzheimer´s disease (LINK). Our next deep dive takes us into Autism Spectrum Disorder (ASD).
The term refers to a diverse group of conditions related to the development of the brain that a large variety of symptoms can characterize. The core symptoms include
- problems in social interaction / communication
- restricted and repetitive behaviors
It is often accompanied by different co-morbidities, including attention deficits, impaired sleep, epilepsy, movement and sensory abnormalities, and hyperactivity. Some people with autism can live independently, while others have severe disabilities and require life-long care and support [1].
The WHO estimates that, on average, approx. 1 out of 100 children worldwide might have ASD [2]. The prevalence is rising rapidly, highlighting the disease as a global pandemic that – like dementia / Alzheimer´s disease – affects not only the actual patients but also their social network, particularly the caregivers [2].
Currently, available treatment strategies are not well supported with regard to their long-term effects and only provide short-term improvements.
In this context, tPBM emerges as a novel treatment option that can improve many pathologies underlying the disease. It was only relatively recently that the first small PBM- studies on humans with ASD were published.
First human study (2018): tPBM for children and adolescents with ASD aged 5–17 years
Leisman et al. [3] published the first study on humans in 2018. They treated twenty-one children and adolescents aged between 5 and 17 years
- with eight 5-min procedures over four weeks
- with 635nm real medical lasers (as opposed to LEDs) with a power output of 15mW.
- The intervention was administered to the base of the skull and temporal areas.
The researchers compared the changes in behavior to a control group by evaluating the participants with the “Aberrant Behavior Checklist (ABC)” and different other subscales at the beginning of the study, after two weeks of treatment, at the end point of the study after four weeks, and lastly, after eight weeks to assess whether changes maintained over time.
The treatment group patients showed reduced irritability and reduced other symptoms and behaviors associated with ASD after 2, 4, and also eight weeks, indicating that positive changes were maintained even after the end of the intervention. Based on my personal observations and general understanding of PBM, 6-10 weeks is a realistic time for the positive effects to maintain. Ideally, the treatment should be ongoing.
Second human study (2022): tPBM for children and adolescents with ASD aged 5–15 years
Pallanti et al. [4] published another study on treating twenty-one children between 5 and 15 years (average 9,1) with ASD. Here is a detailed description of their protocol:
- The participants received transcranial PBM in the convenience of their homes with a wearable headset five times a week for 6 months.
- The wavelength was 810nm, and the researchers used LEDs.
- On each of the five weekly treatment days, the participants received two therapies: One in the morning with the light pulsed at 10Hz (“alpha protocol”) and one in the evening with the light pulsed at 40Hz (“gamma protocol”). I will soon write a separate article about the potential and relevance of tPBM- induced modulation of neural oscillation.
- The therapy was administered to the subdivisions of the default mode network (DMN); the medial prefrontal cortex, the precuneus area, and the left and right angular gyrus.
- Additionally, the participants received intranasal treatments for delivering systemic effects, also with 810nm.
- One session took 20 minutes. During the sessions, the children were allowed to engage in “stimulating activities” such as drawing, reading, or playing games.
- The energy and power parameters are summarized below.
The study results included the following:
- a reduction in cognitive and behavioral rigidity
- an increase in sleep quality
- an improvement in attention
- a relevant reduction in noncompliant behavior.
- reduced stress of caregivers / the family due to these improvements
Recalling that all treatments were administered at home, the study also highlighted the practicality and safety of the therapy.
Third human study (2022): tPBM for adults aged between 18 and 59 with ASD
There is also a small but promising study on adults with ASD [5]. Ten participants received twice-weekly tPBM over a period of eight weeks.
The results included
- improved social awareness
- improved social communication
- improved social motivation
- reduced restricted / repetitive behavior
How does tPBM work on Autism Spectrum Disorder?
Even though extensive efforts were made to study the physiological mechanisms behind ASD, there is still a significant lack of knowledge in our current understanding. What is clear is that ASD can be understood as a group of disorders with complex etiology, that may involve genetic, and environmental causes as well as lesions.
Yenkoyan et al provided a review of studies that examined the pathophysiology of autism spectrum disorders [6]. Emphasizing that the whole puzzle is not yet solved, a (simplified) understanding of the mechanisms behind ASD can be summarized as follows:
- imbalanced functional connectivity, especially between areas associated with higher cognitive functions like speech and communication, cognition, social interaction, personality, task switching, self-control, and working memory.
- imbalanced synaptic transmission due to synaptic molecules and proteins becoming dysfunctional
- neuroinflammation due to an increased release of proinflammatory cytokines by microglia and astrocytes
- mitochondrial dysfunction, leading to a general lack of cellular energy and impaired cellular processes of different kinds
- oxidative stress, ultimately leading to dysfunctional neuronal activity and, subsequently neuronal death
- pathologically elevated levels of growth factors such as BDNF (brain-derived neurotrophic factor), leading to impaired homeostasis and, subsequently synaptic dysfunction and cell toxicity.
- an altered gut microbiome, which can alter brain connectivity and networks
Considering the mechanisms of tPBM about which I recently wrote (LINK), it may be hypothesized that tPBM can improve many, if not all, of these abnormalities. Specifically, the intervention can enhance mitochondrial function, reduce inflammations and oxidative stress, and restore homeostasis and functional connectivity across the brain. (LINK)
Furthermore, PBM applied to the gut area may help restore the gut microbiome.
Hamilton et al. [7] recently published an article on how tPBM can work on ASD. I strongly recommend it if you want to read about this in more detail. This is the link.
Testing these hypotheses with animal models
To test these hypotheses, animal models can be very useful. Even though those models cannot perfectly represent the highly complex human ASD conditions, they can nevertheless mimic some of the major features of ASD.
In this context, a recent Autism mouse model [8] provided strong support for one of the proposed mechanisms of tPBM in ASD: The intervention effectively reduced neuroinflammation by attenuating the increased proinflammatory activity of astrocytes and microglia. Furthermore, tPBM attenuated many of the pathological behaviors observed in the valproic acid-induced ASD mouse model.
A summary and outlook: What might be practical recommendations for ASD patients?
Even though there is a clear need for larger clinical trials, the existing studies and exploration of the mechanisms that underly ASD suggest that tPBM can be able to provide effective support for patients and their caregivers. Particularly the lack of effective holistic treatments that can do more than just treat specific ASD symptoms and the practicality and safety of the therapy provide strong reasons that tPBM should be used for patients with ASD.
Disclaimer
I’m not a medical professional, and the above is not meant as medical advice; I’m merely sharing my personal understanding of the subject.
Literature
[1] Fuentes, J.; Hervás, A.; Howlin, P. (ESCAP ASD Working Party) ESCAP Practice Guidance for Autism: A Summary of Evidence-
Based Recommendations for Diagnosis and Treatment. Eur. Child. Adolesc. Psychiatry 2021, 30, 961–984.
https://pubmed.ncbi.nlm.nih.gov/32666205/
[2] https://www.who.int/news-room/fact-sheets/detail/autism-spectrum-disorders#:~:text=It%20is%20estimated%20that%20worldwide,figures%20that%20are%20substantially%20higher.
[3] Leisman, G., Machado, C., Machado, Y., & Chinchilla-Acosta, M. (2018). Effects of Low-Level Laser Therapy in Autism Spectrum Disorder. Advances in experimental medicine and biology, 1116, 111–130. https://doi.org/10.1007/5584_2018_234
https://pubmed.ncbi.nlm.nih.gov/29956199/
[4] Pallanti, S., Di Ponzio, M., Grassi, E., Vannini, G., & Cauli, G. (2022). Transcranial Photobiomodulation for the Treatment of Children with Autism Spectrum Disorder (ASD): A Retrospective Study. Children (Basel, Switzerland), 9(5), 755. https://doi.org/10.3390/children9050755
https://pubmed.ncbi.nlm.nih.gov/35626932/
[5] Ceranoglu, T. A., Cassano, P., Hoskova, B., Green, A., Dallenbach, N., DiSalvo, M., Biederman, J., & Joshi, G. (2022). Transcranial Photobiomodulation in Adults with High-Functioning Autism Spectrum Disorder: Positive Findings from a Proof-of-Concept Study. Photobiomodulation, photomedicine, and laser surgery, 40(1), 4–12. https://doi.org/10.1089/photob.2020.4986
https://pubmed.ncbi.nlm.nih.gov/34941429/
[6] Yenkoyan, K., Grigoryan, A., Fereshetyan, K., & Yepremyan, D. (2017). Advances in understanding the pathophysiology of autism spectrum disorders. Behavioural brain research, 331, 92–101. https://doi.org/10.1016/j.bbr.2017.04.038
https://pubmed.ncbi.nlm.nih.gov/28499914/
[7] Hamilton, C., Liebert, A., Pang, V., Magistretti, P., & Mitrofanis, J. (2022). Lights on for Autism: Exploring Photobiomodulation as an Effective Therapeutic Option. Neurology international, 14(4), 884–893. https://doi.org/10.3390/neurolint14040071
https://pubmed.ncbi.nlm.nih.gov/36412693/
[8] Kim, U. J., Hong, N., & Ahn, J. C. (2022). Photobiomodulation Attenuated Cognitive Dysfunction and Neuroinflammation in a Prenatal Valproic Acid-Induced Autism Spectrum Disorder Mouse Model. International journal of molecular sciences, 23(24), 16099. https://doi.org/10.3390/ijms232416099
https://pubmed.ncbi.nlm.nih.gov/36555737/
[9] Hamblin M. R. (2022). Could Photobiomodulation Treat Autism Spectrum Disorder?. Photobiomodulation, photomedicine, and laser surgery, 40(6), 367–369. https://doi.org/10.1089/photob.2022.0051
https://pubmed.ncbi.nlm.nih.gov/35613405/