Despite a wide-ranging interest in performing clinical research for bioelectronic medicine applications, there are no open-architecture and open-source implantable systems for autonomic nerve stimulation and recording available to researchers. As a result, progress towards bioelectronic clinical therapies is hampered by the significant technical, regulatory, and financial hurdles faced by researchers to gain access to the few commercial implantable neuromodulation technologies for early clinical studies. The few clinical closed-loop implantable neuromodulation systems presently available are not suitable for the many bioelectronic medicine applications envisioned, as they lack key functional modules for accessing the autonomic nerves; moreover, most use closed architectures (e.g., the use of custom ASICs instead of commercial over-the-shelf components) and proprietary software, limiting the ability to adapt such systems for different clinical indications. To address these shortcomings, the overall objective of this HORNET OpenNerve Platform project is to develop and disseminate a fully open-architecture and open-source implantable system for autonomic nerve stimulation and end-organ sensing. In this administrative supplement, we will perform short-term and long-term validation of the OpenNerve Platform functionality in large animals for closed-loop sacral nerve stimulation for treatment of chronic constipation. The OpenNerve Platform includes an external charger and controller, implantable pulse generator, and an assortment of implantable leads for nerve stimulation and internal organ sensing. The use of sacral nerve stimulation for treating chronic constipation was selected based on potential clinical indications that are of interest to the NIH SPARC program.

This administrative supplement application is related to parent award U41 NS129514 “HORNET OpenNerve Platform” which aims to develop and disseminate an open-architecture and open-source implantable system for autonomic nerve stimulation and recording system to support clinical research for bioelectronic medicine applications. The objective here is to perform short- and long-term validation of the OpenNerve Platform functionality in large animals for closed-loop sacral nerve stimulation and for treatment of chronic constipation. Studies will include the implanted OpenNerve Platform components: (1) implantable pulse generator, (2) implantable leads for nerve stimulation; (3) implantable leads for recording muscle activity (4) implantable leads for strain sensing, and (5) implantable leads for pH and Acetylcholine sensing.