🎓 Qualification : PhD • 🤝 Employment type : 3 year contract • 📍 Location : Grenoble, France
CEA-Leti is seeking an accomplished junior investigator to bring new insights to the institute’s research on closed-loop implantable multi-system sensing devices for neurological disease management. The winner of this three-year Science Impulse fellowship will manage their own groundbreaking research project and have an opportunity to work with CEA and other Grenoble-based research teams.
Background
Chronic neurological diseases like Alzheimer’s, Parkinson’s, ALS, and epilepsy affect tens of millions of people worldwide. Supportive therapies are helping more and more patients, but the lack of disease-modifying treatments persists. Some treatments—such as for Parkinson’s and drug-refractory epilepsy—are simply not effective enough. This is mainly due to a limited understanding of these diseases and the related pathophysiology, and sluggish development of integrated technologies and solutions for diagnosis, treatment, and monitoring. Recently developed solutions that combine advanced sensors to measure biomarkers with algorithms and software to enable closed-loop medical decision making and disease monitoring, could dramatically improve the management of these diseases. Implantable biosensors, for example, have the capacity to generate a continuous stream of data down to a single target analyte, enabling the monitoring of analyte levels over time without any intervention from the patient or the clinician.
Scope and applications
Parkinson’s disease (PD), a neurodegenerative syndrome involving multiple motor and non-motor neural circuits in the basal ganglia1, could benefit from this type of implantable solution. PD patients are currently treated using L-Dopa derivatives and, for advanced cases, deep-brain stimulation (DBS)2. DBS involves the delivery of a predetermined (open-loop) program of electrical stimulation to deep-brain structures via implanted electrodes connected to an implantable pulse generator. DBS is highly effective at treating symptoms, but it does not cure the disease. A more recent treatment, photobiomodulation, whose neuroprotective effects have been shown to slow down PD progression in preclinical trials3, is also encouraging.
Implantable biosensors could make both DBS and photobiomodulation more effective by providing quantitative disease progression indicators that could be used to adapt stimulation to individual patients’ needs. Multiple biosensors could be integrated to measure specific local analytes, enabling continuous monitoring and adjustment of treatment. Treatment outcomes could also be calculated. These new technologies could be integrated into new implantable devices capable of changing disease progression. One example is the photobiomodulation device currently being tested in a clinical trial (NCT042615694) in Grenoble.
Drug-refractory epilepsy (DRE) is another disease that could benefit from implantable biosensors. Epilepsy is a common chronic neurological disorder characterized by spontaneous recurrent seizures. DBS has emerged as an important treatment option when surgery is contraindicated or ineffective6. Unlike PD, epileptic seizures are discrete events, and implantable biosensors that measure selected markers near the epileptic zone could make on-demand treatment a reality, dramatically improving the management of the disease, without the side effects of continuous open-loop treatments. Another potential and major application could be a biosensor integrated into a diagnostic stereo-electroencephalography (sEEG) lead to help map the epileptic zone accurately before surgery.
Job description
CEA-Leti is seeking an accomplished junior investigator with expertise in neuroscience and neuromodulation technologies to run a three-year project at the institute’s Clinatec division. Interested candidates should submit a compelling research proposal addressing the exploration of a new generation of implantable closed-loop sensing devices. The overriding objective should be to transition from no-feedback continuous treatment to high-efficacy, on-demand electrical or photonic stimulation controlled by local biomarker measurements. Projects with a clear ambition of developing biosensors for integration into autonomous implants for neurological disease applications will be preferred. Marked progress toward a clinical solution will be expected.
Candidates must bring innovative ideas and demonstrate an ability to work with CEA-Leti’s multidisciplinary teams. Candidates will be expected to conduct the research independently but will have access to CEA-Leti’s portfolio of NIR light sensing, biophysical monitoring (regional tissue oxygenation, glucose), and other technologies, and will have the support they need to utilize CEA-Leti facilities and microelectronics and optoelectronics-driven developments.
Specifically, the candidate selected will be paired with an engineer and receive support from neuroscientists and preclinical and clinical researchers at CEA-Leti.
Before the technologies for a future closed-loop implant can be selected, the candidate will need to complete a detailed assessment, for both PD and DRE, of the pertinent and measurable biomarkers, the brain regions that will need to be accessed, implantability, and other clinical aspects. For both PD and DRE, for example, this will include in vivo trace change assessments of neurotransmitter calls for the development of miniaturized ultra-sensitive implantable sensors for glutamate for instance, which is less lesional than brain microdialysis.
This work willform the basis for specifications for the development of the implant using technologies available at CEA-Leti and, possibly, other technologies.
Biblio references
- Lang AE, Lozano AM. Parkinson’s disease. First of two parts. N Engl J Med. 1998;339(15):1044-1053. doi:10.1056/NEJM199810083391506
- Benabid A, Chabardes S, Seigneuret E, et al. Complications of STN surgery for PD in 300 patients operated over 13 years. In: MOVEMENT DISORDERS. Vol 21. WILEY-LISS DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA; 2006:S606–S606.
- Darlot F, Moro C, El Massri N, et al. Near-infrared light is neuroprotective in a monkey model of Parkinson’s disease. Ann Neurol. Published online October 11, 2015. doi:10.1002/ana.24542
- https://clinicaltrials.gov/ct2/show/NCT04261569
- Engel J. What can we do for people with drug-resistant epilepsy? The 2016 Wartenberg Lecture. Neurology. 2016;87(23):2483-2489. doi:10.1212/WNL.0000000000003407
- Bouwens van der Vlis TAM, Schijns OEMG, Schaper FLWVJ, et al. Deep brain stimulation of the anterior nucleus of the thalamus for drug-resistant epilepsy. Neurosurg Rev. 2019;42(2):287-296. doi:10.1007/s10143-017-0941-x
- Sacchettoni SA, Abud JP, Torres N, et al. Dynamic Cerebral Microdialysis during Pallidotomy and Thalamotomy in Parkinson’s Disease: A Preliminary Neurochemical Study. Open J Mod Neurosurg. 2020;10(2):284-296.E
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