DS04 - Vie, santé et bien-être

Adaptive, subject-specific Vagus Nerve Stimulation – AdaptVNS

Submission summary

Vagus nerve stimulation (VNS) is an approved clinical therapy for medically refractory epilepsy and depression. More recently, VNS has been proposed as a promising therapeutic approach for other pathologies such as heart failure, cardiac arrhythmia, inflammation and auto-immune diseases. One common difficulty currently encountered in all these established or promising clinical applications is to deliver an efficient therapy, while minimizing side effects. This is a particularly complex problem in the case of VNS, since a typical stimulation pattern consists of a set of biphasic pulses, characterized by several parameters, delivered through different electrode configurations. Moreover, the effects of VNS are poorly known and complex to study, since they involve many different organs and physiological functions and may change through time, due to neural or organ remodeling.

Due to this complexity, current VNS technology is applied using fixed parameters obtained from limited, non-optimal manual titration and this simplistic approach may explain the lack of effect or the intolerance to the therapy. Although many efforts have been performed recently to propose closed-loop VNS methods, the proposed algorithms remain simple, limited to the modulation of one parameter and without a clear definition of the appropriate control variables. Furthermore, current electrode technologies provide a poor spatial resolution for stimulation and a low signal-to-noise ratio for neural recording, also limiting the development of advanced closed-loop approaches. We hypothesize that the use of an automated, closed-loop and subject-specific method for VNS parameter optimization, integrating new electrode technologies and new knowledge of the underlying physiology, may lead to an improved outcome for VNS patients and to address new therapeutic applications.

The main objective of this project is thus to propose such novel data processing methods and electrode technologies, allowing for a closed-loop, subject-specific optimization of VNS therapy. Although the proposed methods and technologies will be generic, a second objective is to explore, through extensive in-silico, in-situ and in-vivo experimentations, the usefulness of the proposed system on a promising therapeutic target for VNS: the prevention of Sudden and Unexpected Death in Epileptic Patients (SUDEP). This second objective requires 1) the early detection of the potential occurrence of a SUDEP event and 2) the application of an original acute, adaptive VNS, to block the propagation through vagal efferent pathways, in order to prevent bradycardia and respiratory arrest.

This project is organized in 6 work-packages. WP1 concerns project management. Two WP will be focused on technical developments: WP2 for data processing, modelling and control methods and WP3, focused on novel electrode technologies. A prototype neurostimulation system integrating these technologies will be developed in WP4. Finally, WP5 and WP6 will address the in-situ and in-vivo animal experimentations required for this project.
AdaptVNS is an ambitious project, that we consider however feasible, on the basis of progress achieved in recent years by the consortium and on their available intellectual property (5 patents). Although this project presents some risks, it has a high potential of societal and industrial impact. If this project is successful, the final product will be a complete, functional, neuromodulation system prototype, integrating advanced closed-loop methods and organic electrode technologies. To our knowledge, there is no equivalent system today. Also, new ways for preventing SUDEP will be investigated. Such results may open new ways to optimally deliver VNS on current target clinical applications, to provide novel therapeutic functions, but also, to renew research on novel VNS therapies which are not always effective when delivered with standard technologies (heart failure, antiarrhythmic therapies, etc).

Project coordination

Alfredo Hernandez (LABORATOIRE TRAITEMENT DU SIGNAL ET DE L'IMAGE (LTSI))

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

INS Institut de Neurosciences des Systèmes
LTSI LABORATOIRE TRAITEMENT DU SIGNAL ET DE L'IMAGE (LTSI)

Help of the ANR 469,207 euros
Beginning and duration of the scientific project: January 2018 - 36 Months

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