Periodic Reporting for period 3 - EPI-Centrd (Epilepsy Controlled with Electronic Neurotransmitter Delivery)
Reporting period: 2020-03-01 to 2021-08-31
The technical goal (WP1):
Work performed to the end of the previous period on the technical goal has resulted in the design and fabrication of an integrated probe for the therapeutic treatment of epilepsy. Essentially the technical goal of EPI-Centrd had been successfully achieved, however, as stated at the time, there remained much room for improvement in further devices iterations.
As seen in the updated publication list, an advanced version of the device is now published and in operation using a fully-non-invasive technology (a patent for the new technology has additionally been filed, Patent EP 21306447).
The neuroscientific goal (WP2):
This goal is separated into 4 sub-goals, 1) in vitro Testing: Can the new probes control anything pathophysiological?, 2) in vivo Testing I: Can the new probes control activity more clinically-relevant? (Anesthetized rodent testing), 3) in vivo Testing II: Can the new probes control activity more clinically-relevant? (Freely-moving rodent testing), 4) Clinical Operating Room with Human Patients: Can the new probes control pathological activity in patients with drug-resistant epilepsy?.
Work performed to the end of the previous period on the neuroscientific goal had completely addressed the first two points, namely that the new devices control epileptiform activity in vitro, and in vivo in anesthetized rodents. Future activities were necessary to have a closed-loop system and reservoir (under the skin, in skullcaps) for implementation in freely-moving rodents to address the third point and, if successful, preliminary clinical work to address the fourth point (WP3). As mentioned above, the completely non-invasive system developed in this reporting period has eliminated the necessity for the reservoir system. Details of the new devices can be found in the latest publications from this year (Missey et al., Frontiers in Neuroscience, 2021; Acerbo et al., Frontiers in Behavioral Neuroscience, 2021; and Missey et al., Journal of Neuroengineering, 2021).
Given the rapid success, and publications, from the work performed to the end of this period, it is unlikely that the closed-loop intervention in freely-moving rodents will be a problem to achieve by the end of the project. Current work involves a two-step model of freely moving epileptiform activity to approach clinical relevance, namely kindled rodents to create temporally on-demand seizures with spatially fixed foci, and lesioned rodents to create temporally unknown seizures with spatially fixed foci. Seizures with temporally unknown origin and with spatially unknown origin (generalized seizures) will not be investigated, as the device is designed for surgically intractable focal epilepsies. Socio-economically, the majority of surgically intractable epilepsies are focal epilepsies. The wider societal implication of a successful device, is to allow patients with surgically intractable focal epilepsies to live without fear as the condition will be controlled with the device developing in this project.