Since the foundation was established in 2017, much has happened regarding vagus nerve stimulation research. We at the foundation are proud to have been able to contribute to this development.
This is what we have been able to do thanks to all the generous donations:
COPD (Chronic Obstructive Pulmonary Disease)
In Sweden, it is estimated that up to 700 000 people have COPD. The disease is characterized by a constant decrease in airflow in the lungs due to narrowing of the outermost, thinnest bronchi, which makes it difficult to oxygenate the blood. Simply put, patients suffer from constant shortness of breath.
The dominant cause of COPD is smoking – almost 90% of all people who get COPD are, or have been, smokers for a long time. COPD cannot be cured, but exercise and bronchodilators can improve quality of life and maintain lung capacity. The disease is individual, and some people have no major problems while others gradually deteriorate – often with a fatal outcome.
The study was conducted in 2017–2018 at St. Göran’s Hospital in Stockholm under the direction of Karin Sandek, a specialist in internal medicine with a focus on lung diseases and with a doctoral thesis on COPD. The study included 12 patients with pure COPD, i.e. without chronic bronchitis or asthma. 9 patients completed the study. The patient group consisted of both men and women aged 59 to 79 years with COPD of severity 2–3 on an MRC scale (MRC is a questionnaire where the degree of dyspnea, or shortness of breath, is measured/estimated by the patient themselves on a 5-point scale).
The patients received a total of 10 INMEST treatments, 3 per week for just over 3 weeks.
The results showed that:
- 8 out of 9 patients estimated that their COPD was improved after the treatment.
- 4 out of 9 patients had at least one step improvement on the 5-point MRC scale.
- On average, the improvement in the 6-minute walk test was 4.5% (18 meters) but 4 patients had an improvement of up to 10–20%.
- 4 out of 7 patients showed significant improvement in lung capacity (100 ml or more) measured by spirometry.
Notably, the patients described that improvement began to occur after 6–7 treatments out of a total of 10 they received. Based on the knowledge we have today, it is likely that an increased number of treatments would further enhance the results.
Subjective improvement in breathing was described by some patients to last many months after the end of treatment.
Since the COPD study was too small to demonstrate with statistical certainty a positive effect of INMEST, the idea was to continue with two larger studies – one with COPD patients and one with COPD/asthma. Unfortunately, it proved very difficult to find patients with only COPD, which meant that further studies were put on hold in order to be able to continue when suitable patient groups were found.
Our goal is to continue the studies in 2025, either by ourselves or in collaboration with another research group. This study is planned to consist of 100 patients who will receive 3 treatments over a period of at least 6 weeks, i.e. 18 treatments. The study should be placebo-controlled.
Interesting observation
In the COPD study mentioned above, three patients were examined with ultrasound of the heart, focused on the pulmonary circulation. This showed that INMEST treatment lowered the pressure in the pulmonary circulation to normal levels. It is well known that COPD patients have elevated pressure in the pulmonary circulation.
Possibly, the normalization of the pressure is an explanation for the fact that the COPD patients felt better, and this can thus be an important piece of the puzzle in order to understand the disease and find effective remedies. Another possible explanation is that in COPD there is usually a chronic inflammation that causes swelling in the affected tissue (airways). Possibly the known anti-inflammation effect of vagus nerve stimulation with INMEST reduces swelling in the airways, whereupon air flows more easily to and from the lungs.
Dry Eye Disease (DED)
Dry eyes is a common condition that affects 10–15% of all adults and the prevalence increases with age. The cause of the problems can be various diseases but can also have other causes. Foundation members Jan-Erik Juto and Fredrik Källmark concluded that INMEST could potentially function as a treatment for DED, which led to the initiation of a study.
Dry eye pilot study
In 2018, a randomized double-blind study led by Fredrik Källmark was started at the Källmark Clinic. A total of 36 patients were initially included. Half of the patients received the real treatment and half received a placebo treatment three times a week for two weeks.
An analysis showed promising results for the group that received active treatment, which is why it was decided that the entire group would receive 6 more treatments, so that all patients would receive at least 6 active treatments each. The study was expanded and ultimately 43 patients were included, of which 35 completed during 2018–2019.
New analysis of data showed enhanced efficacy after increasing the number of patients and extending the treatment period with INMEST. A decision was made to increase the number of patients to 100. The amendment application was submitted to the ethics committee and approved. However, the Covid-19 pandemic meant that the expanded study could only be started in the fall of 2021 and completed in 2022. A total of 72 patients were included, of which 65 completed the study.
The results show that INMEST on 6 occasions reduced dry eye symptoms and that the effect was enhanced after 12 treatments. As measured by the primary outcome variable (Ocular Surface Disease Index, OSDI), symptoms were reduced by an average of 40% after four weeks of regular INMEST. The study is not published.
Dry eye follow-up study
In a larger new study, led by Abilion Medical Systems AB, patients with dry eyes were included where they were treated regularly with INMEST at home. The study is double-blind, randomized, placebo-controlled. The study was conducted at various clinics focused on the treatment of dry eyes in Sweden and Denmark. The study is therefore approved by the Swedish Medical Products Agency and ethics committees in both Sweden and Denmark.
The INMEST Foundation is co-funding this study, which includes approximately 100 patients and has been ongoing since autumn 2023. Half of the patients are treated with INMEST and half with placebo three times a week for six weeks. Follow-up ends three months after the last treatment. The study is no longer recruiting more patients and publication of the results is preliminary planned for spring 2025.
Chronic Fatigue Syndrome (ME/CFS) Study
ME/CFS, also known as chronic fatigue syndrome, is a serious, systemic, chronic illness that significantly impairs the quality of life of those affected. The disease often debuts at the same time as an infection.
The study, which included 31 patients, was a double-blind, randomized, placebo-controlled study conducted in 2018–2019 at the Neurological Rehabilitation Clinic at Stora Sköndal, Stockholm. It was initiated by senior physician Dr. Per Julin and Petter Brodin, who is a pediatrician and professor of pediatric immunology. INMEST was administered by staff at the clinic.
Patients received either active INMEST or placebo twice a week for the first four weeks, after which all patients received active INMEST twice a week for the subsequent four weeks.
No treatment effect was seen on fatigue. However, both the group that initially received placebo and the group that always received active INMEST reported reduced disease symptoms, as measured by a questionnaire. In the questionnaire, patients rated 14 common ME symptoms on a 5-point scale (none, mild, moderate, severe and unbearable): tender lymph nodes; palpitations; fever; orthostatic dizziness; irritable bowel syndrome; sleep disturbances; numbness and paresthesia; joint pain; general pain; body aches; difficulty concentrating; memory problems; chills and sweating and headache.
The improvement measured by this scale was approximately twice as great in the group receiving active INMEST compared to those receiving placebo, during the first half of the study. During the remainder of the study when all patients received active INMEST, both groups continued to improve, and again the improvement was more pronounced in the group that received active INMEST throughout. The symptom relief in the group that received active INMEST at all times was from the beginning to the end of the study (after 16 treatments with INMEST) ~30% and this was a statistically significantly more pronounced symptom reduction compared to the group that received placebo during the first half of the study (p=0.00003). The symptom relief seen in both groups after the treatment period was maintained over the following three months.
To study how repeated INMEST treatment affects the body, blood samples were taken before the start of the study, after four weeks of treatment, and after eight weeks of treatment with INMEST. A series of advanced analyses were performed on the blood samples. Among other things, the composition of immune cells and their surface structures were studied using mass cytometry. In addition, proteins in the blood were examined with the help of Olink analyses using three so-called panels measuring proteins of importance in inflammation and for cell metabolism and functioning of the nervous system. So-called mRNA sequencing was also done to determine to what extent different genes were expressed.
The study showed that the most upregulated gene with INMEST was UBE2H, which stimulates ubiquitin-mediated degradation of dysfunctional proteins. In addition, INMEST increased the gene expression of SIRT1, a response pathway that counteracts oxidative stress. There was also an improvement in energy metabolism in so-called mononuclear cells (which include several types of cells in the immune system). In addition, IL-17A was one of the proteins that decreased the most after INMEST treatment, and IL-17A is believed to contribute to chronic inflammation.
Finally, with INMEST, an increased proportion of specific regulatory T cells and a decreased proportion of effector cells were observed. T cells are important for maintaining balance in the gut, and effector cells are known to interact with microbes in the gut and promote inflammation.
This study is published in 2023 in Oxford Open Immunology and can be read in full for free at:
https://academic.oup.com/ooim/article/4/1/iqad003/7126430
Study of induced radiation damage to the brain in the treatment of brain tumors in children
Children who develop brain cancer at a young age and have to undergo radiation therapy to the brain often have permanent brain damage as a result of the long-term inflammation that occurs as a result of the radiation. The initial inflammation that occurs after brain irradiation is beneficial for the patient. However, the radiation also causes continued inflammatory activity in the brain that is harmful to cognitive development (mental development). Therefore, children under the age of 4 are not irradiated.
When Jan-Erik Juto, co-inventor of INMEST, met Klas Blomgren, professor and chief physician in pediatrics at Astrid Lindgren Children’s Hospital at Karolinska University Hospital, a discussion arose about INMEST’s anti-inflammatory effect. This led to the initiation of two studies to investigate whether treatment with INMEST can reduce inflammation in the brain after radiotherapy. Grants for the studies were applied for and granted by the Swedish Childhood Cancer Fund.
The study began in 2017 at Karolinska Insitutet. The research leader is Klas Blomgren.
This type of early studies cannot, for obvious reasons, be done on children but are primarily done on rats and mice. The studies that have now been conducted demonstrate a significant decrease in activity in microglia cells (a strong indicator of reduced inflammation in the brain) after repeated (3–4) treatments with INMEST. The treatments were given under anesthesia for two weeks after radiation therapy with 10 Gray was given. The results are interpreted as a strong signal for reduced inflammation in the brain after treatment with INMEST.
The second project studied inflammation in a rat model of brain damage in the newborn period (perinatal asphyxia). The animals were housed in an oxygen-deficient environment according to this study protocol. The study showed that inflammation was reduced by INMEST and neurological function was improved by the treatments in females, but not in males.
The two different projects are in the final stages of manuscript writing, with Klas Blomgren’s research group expecting to publish the results in 2025.