Authors :
Guadalupe Zepeda, BS – NeuroOne
Maria Porto Cruz, Ph.D. – NeuroOne
Maria Vomero, Ph.D. – NeuroOne
Su-youne Chang, Ph.D. – Mayo Clinic Rochester
Jiwon Kim, BS – Mayo Clinic Rochester
Inyong Kim, Ph.D. – Mayo Clinic Rochester
Filip Mivalt, PhD – Mayo Clinic Rochester
Alfonso Chavez, BS – NeuroOne
Mary McNeil, MS – NeuroOne
Nidhi Kalia, BS – NeuroOne
Camilo Diaz-Botia, Ph.D. – NeuroOne
Gregory Worrel, MD,PhD – Mayo Clinics
Presenting Author: Aura Kullmann, PhD – NeuroOne
Rationale:
Stereoelectroencephalography (sEEG) evaluation is part of the diagnosis for patients with drug-resistant epilepsy. The sEEG electrodes are FDA-cleared for temporary (< 30 days) neural activity monitoring, recording and stimulation. In 2023, an FDA-cleared radiofrequency ablation (RFA) feature was added to the sEEG platform, enabling real-time, temperature-controlled focal ablations.
We are advancing this platform by developing an sEEG-based drug delivery system designed for convection-enhanced delivery (CED). Three device sizes have been developed to accommodate brain sizes across species, from rodents to large animals and humans.
Methods:
Device characterization was performed using electrochemistry. CED was tested in 0.6% agarose gel. In vivo testing was conducted in rodents and swine. sEEG electrodes were stereotactically implanted into the hippocampus (HC) and putamen (PUT). Penicillin (5000 units/µL) was infused to modulate neural activity. Diffusion volume (Vd) was evaluated using MRI with gadolinium (Gd) contrast in swine and histological analysis in rodents. Results:
Bench testing confirmed impedance ranges suitable for in vivo applications. CED was demonstrated at infusion rates of 0.5–15 µL/min and infused volumes (Vi) of 60–300 µL, with Vd/Vi ratio of 2.7-3.4. Penicillin infusion reliably induced seizure-like activity in both rodent and swine hippocampi. MRI demonstrated localized Gd diffusion in swine PUT and HC, while histological analysis confirmed confined Vd in rodent brain tissue.
Conclusions:
This integrated sEEG-based platform, capable of neural monitoring, recording, stimulation, and targeted drug delivery, enables cross-species translational research using a single device. Its scalable design supports consistency in evaluating drug efficacy, dosing, toxicity, and mechanisms of action from preclinical to clinical stages. This approach may reduce late-stage drug development failures and improve therapeutic outcomes.
Moreover, combining multiple functionalities in one sEEG-based device platform has the potential to increase the accuracy of diagnosis and provide treatment within one single surgical procedure.
Funding: NeuroOne