Targeting peripheral nerves: a method for therapeutic modulation of inflammatory disease with non-invasive temporal interference

Project Information

TREATMENT

Grant agreement ID: 101101040

DOI

10.3030/101101040

Project closed

EC signature date 16 March 2023

Start date 1 April 2023

End date 30 September 2024

Funded under

• European Research Council (ERC)

Total cost

No data

EU contribution

€ 150 000,00

Coordinated by

FAKULTNI NEMOCNICE U SV ANNY V BRNE
Czechia

Periodic Reporting for period 1 - TREATMENT (Targeting peripheral nerves: a method for therapeutic modulation of inflammatory disease with non-invasive temporal interference)

Reporting period: 2023-04-01 to 2024-09-30

Summary of the context and overall objectives of the project

Inflammatory diseases, including rheumatoid arthritis, Crohn’s disease, and cardiovascular conditions, affect millions worldwide and are among the leading causes of disability and death. Current treatment options, predominantly pharmaceutical interventions, often lack precision, leading to unwanted side effects and limited efficacy in many patients. This gap underscores the urgent need for innovative therapeutic approaches that can target the underlying physiological mechanisms of inflammation with greater specificity and fewer adverse effects. Peripheral nerve stimulation, particularly of the vagus nerve, offers a promising non-pharmacological alternative by leveraging the body’s natural reflexes to regulate inflammation. However, conventional methods for vagus nerve stimulation (VNS) are invasive, requiring surgical implantation of electrodes, which limits accessibility and carries risks such as infection and tissue damage.
The TREATMENT project aims to overcome these challenges by developing and validating a non-invasive temporal interference (TI) stimulation technology. This cutting-edge approach uses high-frequency electrical currents to create precise, focal stimulation of the vagus nerve without the need for surgical implants. By demonstrating the ability of TI stimulation to modulate key physiological parameters, such as heart rate and breath rate, the project lays the groundwork for new therapies targeting inflammatory diseases. In addition to reducing barriers to treatment, this technology holds the potential to transform patient care by enabling earlier interventions, improved comfort, and personalized therapies. The expected impact is a significant step forward in bioelectronic medicine, addressing unmet medical needs and reducing the healthcare burden associated with chronic inflammatory diseases.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The TREATMENT project focused on developing and validating non-invasive temporal interference (TI) stimulation as a revolutionary approach to modulate vagus nerve activity. The team designed and tested a prototype system capable of delivering highly precise electrical stimulation through transcutaneous (skin-based) electrodes. Both wet and dry electrode configurations were evaluated, with a novel grid-based multipolar design introduced to enhance focality and reduce the electrical current required per electrode pair. Human studies demonstrated that TI stimulation effectively modulated key physiological parameters, including heart rate and breath rate, by targeting the right vagus nerve. Importantly, the use of high-frequency kHz-range carrier signals avoided skin sensations commonly associated with traditional amplitude-modulated stimulation, improving participant comfort and usability. This innovation significantly advances the state of the art by achieving the specificity of implanted devices while remaining entirely non-invasive.
A key outcome of the project was the successful demonstration of the technology's efficacy in healthy volunteers, showing its potential to translate into therapeutic applications for inflammatory diseases. The findings included a reduction in the electrical current required for stimulation when using the multipolar electrode grid, enabling a safer and more scalable solution for long-term use. The groundwork was also laid for future studies targeting the left vagus nerve to address inflammatory markers, with promising early results indicating the potential for treating conditions such as rheumatoid arthritis and Crohn's disease. The project’s outcomes establish a robust foundation for further clinical trials and device optimization, paving the way for a new class of bioelectronic therapies with transformative potential in personalized medicine.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The TREATMENT project has delivered groundbreaking advancements in non-invasive neuromodulation through temporal interference (TI) stimulation, surpassing the limitations of existing technologies. Traditional vagus nerve stimulation (VNS) methods rely on invasive surgical implants, posing significant risks and limiting accessibility. TREATMENT demonstrated, for the first time, that TI stimulation can modulate vagus nerve activity with precision and efficacy using entirely non-invasive techniques. The novel multipolar electrode grid developed during the project enhanced stimulation focality while reducing the electrical current required, improving both safety and scalability. By effectively modulating physiological parameters such as heart rate and breath rate in healthy volunteers, the project validated its approach and laid the foundation for therapeutic applications targeting chronic inflammatory diseases. These innovations redefine the potential of bioelectronic medicine, addressing unmet clinical needs with a patient-friendly alternative.
To ensure the further uptake and success of this transformative technology, several steps are required. Future research must focus on large-scale clinical trials to establish efficacy in treating specific conditions like rheumatoid arthritis and Crohn's disease. Demonstration projects targeting inflammatory biomarkers through left vagus nerve stimulation will also be critical. Commercialisation efforts will require sustained access to finance, strategic partnerships with industry stakeholders, and robust intellectual property protection. Regulatory frameworks must adapt to accommodate non-invasive bioelectronic devices, and standardisation efforts will be essential to ensure global adoption. The results of the TREATMENT project include a validated prototype system, novel electrode designs, and strong proof of concept for non-invasive vagus nerve stimulation, setting the stage for commercialization and widespread clinical impact. These advancements have positioned TREATMENT as a leader in the emerging field of bioelectronic medicine.