The 5 year results from the original clinical trial using light therapy for Parkinson's disease has now been published in BMC Neurology. BMC Neurology is one of the world's top leading medical journals, making these results another important breakthrough for Parkinson's disease symptom management.
Before we jump into the details of this clinical trial, it is important to note that this trial, which was the first of its kind and was run in Australia in 2019, had a small cohort. SYMBYX now has much larger trials underway, with bigger cohorts and more analyses, including looking into the gut microbiome changes in more depth. Nevertheless, 5 years on, the results from this original trial still offer some promising results.
The trial design:
The original clinical trial ran in Adelaide, Australia between 2019-2020, with the original results being published in BMC Neurology in 2021. Twelve participants with Parkinson's disease were recruited and treated 3 times per week (eg. Monday, Wednesday and Friday) using a super-pulsed 904 nm infrared laser on the abdomen and neck, a light therapy helmet and a nasal applicator. They were treated initially in clinic, and then continued treatment at home for 1 year. The 904 nm laser treatment took 20 minutes (18 minutes on the gut and 2 minutes on the back of the neck).
The original trial - results after 12 weeks of treatment
The original results were very promising, demonstrating significant improvements in mobility, cognition, dynamic balance, and fine motor skill at 12 weeks and up to 1 year (Liebert et al, 2021). For many people, they saw improvements in a range of their symptoms, though the exact degree of improvement and of which symptom varied from participant to participant.
These early findings showed promise for the effectiveness of light therapy in reducing a number of motor and non-motor Parkinson's symptoms. Stool analyses were also performed before and after 12 weeks, which demonstrated that PBM could also improve the gut microbiome of people with Parkinson's (Bicknell et al, 2022). The gut microbiome is critically linked with Parkinson's disease, and can directly improve or disrupt dopamine levels (Hamamah et al, 2022). It can also contribute to constipation, and affect levodopa absorption, contributing to dyskinesias and "off" periods (Bicknell et al, 2022).
Just like levodopa, light therapy treatment was applied via the gut. Rather than ingesting a pill, the laser is held against the tummy, where it emits painless light into the abdomen. 904 nm infrared laser therapy naturally energises cells to work better, reduces inflammation and oxidative stress, and stimulates the gut microbiome, which has far-reaching effects for our dopamine via the gut-brain axis (Bicknell et al, 2022, Hamamah et al, 2022). You can check out one of our other blog posts for more info on how light therapy works on the gut.
What happened after 2 and 3 years of light therapy?
7 out of the 12 participants continued with their home abdomen-neck treatment and came back for follow-up after 2 and 3 years. For most people, some benefit was still seen after 2 and 3 years, with some symptoms still not returning to pre-treatment test scores. This depended on the individual, but included mobility, walking, balance, fine motor skills including handwriting, sense of smell, and cognition. Mobility, walking and cognition were the symptoms that seemed to maintain the greatest benefit from light therapy at 2 and 3 years follow-up for most participants (Liebert et al, 2023).
5 years and still results!
7 out of the 12 participants continued treating at-home 3 times per week, and agreed to come back for a follow-up assessment after 5 years. Unfortunately, 1 person had been preliminarily diagnosed with another rare neurodegenerative condition, so their results were excluded from the group analysis.
All 7 participants were assessed using the MDS-UPDRS-III (motor section) by a certified neurologist. The MDS-UPDRS-III is considered the gold standard for assessing movement in people with Parkinson’s (Liebert et al, 2024). Participants had all been assessed using the MDS-UPDRS-III by a neurologist before any treatment (baseline), 5 years earlier. As well as the MDS-UPDRS-III, participants were also tested using a number of other motor tests, such as the 10 m walk test, timed up-and-go, spiral test, and a range of balance tests, amongst others.
The non-motor symptoms that were assessed were cognition, sleep and quality of life, using standardised participant and practitioner assessment tools (MoCA, PDSS, and PDQ-39, respectively). It’s also important to note that no participants reported any negative side effects or falls over the 5 years.
Results:
1. Improvements in movement (motor scores):
MDS-UPDRS-III median score was maintained over 5 years. Even though this may not sound like much, this actually may reflect that the therapy is indeed working: people with PD are expected to decline at a rate of 2.4 points per year (12 points over 5 years), in a linear fashion from the first 5 years of diagnosis (Holden et al, 2018). Therefore, the fact that there was no decline in the median score over 5 years may actually be considered an achievement.
Most motor scores were improved at 5 years compared to baseline, with walk speed, stride length and step test significantly improved. The only motor outcome that was not improved was static balance, when tested on the unaffected leg with eyes open (other tests of static balance, such as testing on the affected leg, with eyes open and eyes closed was still improved in most people, however). This is consistent with the pattern that was developing at 2 and 3 year follow-up: that mobility and walking may be the greatest areas of motor improvement, while static balance may be the most variable outcome. At least, that may be what is true for this participant cohort, who were on average 72 years-old by the time of their 5 year follow-up, and may be expected to have declining balance as a factor of aging (Liebert et al, 2024).
2. Improvements in sleep, cognition, and quality of life (non-motor scores):
Cognition (as tested using the MoCA) improved over the 5 years. Cognitive decline is common in people with Parkinson's, particularly as they progress with the condition. In similarly aged people with Alzheimer's, research suggests there is an average rate of decline of 2.39 points in MoCA scores per 12 months, which is a worsening of 11.95 points over 5 years (Miyakawa-Liu et al, 2022). Therefore, to actually improve in cognition scores over 5 years is promising.
Sleep quality also improved for 67% of people (4 out of 6 participants), though the degree of improvement was not as significant as the improvements seen in cognition. PDQ-39 scores, which is a questionnaire participants fill in assessing how the disease affects their quality of life (such as how they feel about going out and socialising, stigma they experience related to the condition, and more) remained unchanged.
3. Individual results:
Parkinson's disease affects everyone a little bit differently, and this was seen in the study results as well. There's no one size-fits-all solution when it comes to treatment, which is why it's always important to consider an interdisciplinary, multi-faceted approach to treatment. At SYMBYX, this is why we always advocate for eating well, exercising regularly, spending time with loved ones, and other positive lifestyle changes, as the combination of these things alongside medications and light therapy can give the best results.
Of the 6 participants who were assessed, 83% (5 out of 6) saw improvements or maintenance of their motor scores when assessed by the neurologist (MDS-UPDRS-III) over the 5 years. 100% (6 out of 6) participants saw improvements or maintenance of their mobility, walking, cognition, and some of the balance tests over 5 years. Sense of smell and sleep improved or was maintained for 67% (4 out of 6) participants over the 5 years.
In general, participants initially improved for the first 12 months of treatment, and then, by continuing treatment, were able to mostly maintain those initial improvements.
A full breakdown of the scores can be seen in the table below (Liebert et al, 2024):
So what can we learn from these 5 year results?
Larger clinical trials are now currently underway around the world to further test these study findings in different cohorts of people with Parkinson's.
As Liebert et al write in the article:
"At this time there are no medications with evidence from Phase 3 trials, that can slow the neurodegeneration that accompanies PD. Thus, there is an urgent need for PD therapies that might slow, halt or even reverse the relentless progression of PD symptoms. Such therapies could help to avoid or at least delay the onset of the more advanced and disabling symptoms of the disease, such as dementia, speech difficulties, and loss of mobility." (Liebert et al, 2024)
Light therapy holds a lot of promise for being a natural and effective adjunct therapy for helping to reduce Parkinson's symptoms, both over the short and the long-term. It's demonstrated consistently now in numerous clinical trials over 40-50 years to have a very high safety profile, meaning it doesn't carry the same risk of side effects such as from medication or surgery. It's accessible, and available for home-use. While it's not yet proven to be a cure, it may offer a natural remedy that can be used alongside medications and DBS, and worked into peoples' daily routines to improve and prolong their life with PD.
We're excited to keep researching the potential benefits of light therapy for improving the lives of people with Parkinson's.
If you still have questions about the latest in research innovations for Parkinson's, please reach out to our team at info@symbyxbiome.com, and our team will be happy to help where we can.
Why does light therapy treat the gut to help Parkinson's disease? Read all about it on our blog.
References:
1) Monica Miyakawa-Liu, Amy K. Feehan, Shannon Pai, Julia Garcia-Diaz Ochsner. Rates of Cognitive Decline in 100 Patients With Alzheimer Disease. Journal Jun 2022, 22 (2) 129-133; DOI: 10.31486/toj.21.0084
2) Liebert, A., Bicknell, B., Laakso, EL. et al. Improvements in clinical signs and symptoms of Parkinson’s disease using photobiomodulation: a five-year follow-up. BMC Neurol 24, 381 (2024). https://doi.org/10.1186/s12883-024-03857-z
3) Liebert A, Bicknell B, Laakso EL, Heller G, Jalilitabaei P, Tilley S, Mitrofanis J, Kiat H. Improvements in clinical signs of Parkinson's disease using photobiomodulation: a prospective proof-of-concept study. BMC Neurol. 2021 Jul 2;21(1):256. doi: 10.1186/s12883-021-02248-y. PMID: 34215216; PMCID: PMC8249215.
4) Bicknell B, Liebert A, McLachlan CS, Kiat H. Microbiome Changes in Humans with Parkinson's Disease after Photobiomodulation Therapy: A Retrospective Study. J Pers Med. 2022 Jan 5;12(1):49. doi: 10.3390/jpm12010049. PMID: 35055364; PMCID: PMC8778696.
5) Hamamah S, Aghazarian A, Nazaryan A, Hajnal A, Covasa M. Role of Microbiota-Gut-Brain Axis in Regulating Dopaminergic Signaling. Biomedicines. 2022 Feb 13;10(2):436. doi: 10.3390/biomedicines10020436. PMID: 35203645; PMCID: PMC8962300.
6) Holden SK, Finseth T, Sillau SH, Berman BD. Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort. Mov Disord Clin Pract. 2018 Jan-Feb;5(1):47-53. doi: 10.1002/mdc3.12553. Epub 2017 Sep 22. PMID: 29662921; PMCID: PMC5898442.
