An adaptive neurostimulator delivering personalised, intelligent DBS therapy for Parkinson’s disease
The challenge
Current pharmacological therapies for Parkinson’s Disease (PD) produce marked improvements in disease symptoms, however very disabling drug-related long-term side effects often appear after several years of disease.
Deep Brain Stimulation (DBS) is an established treatment for advanced PD in which pharmacological approaches no longer control adequately disease symptoms.
However, even after DBS implantation, PD symptoms are subject to clinical fluctuations related to the normal pattern of the underlying disease, bioavailability of medications, or to psychological/activity profile.
Most DBS patients experience suboptimal therapy with some time spent in an overstimulated state leading to stimulation induced side effects and some time spent in an under stimulated state during which symptoms are not sufficiently relieved. Stimulation induced side effects include dyskinesia, speech effects and cognitive impairment
Conventional DBS delivering constant stimulation cannot respond to specific patients’ needs despite repeated hospital visits for stimulation adjustment. In fact, DBS parameters are selected considering a trade-off between control of symptoms and adverse events induced by the stimulation, especially when the patient is under the effects of drugs. In addition, conventional DBS has been associated with complications, such as speech and gait impairments.
Preliminary data collected in the studies conducted with the AlphaDBS System show a marked patient preference for the adaptive DBS (aDBS) stimulation compared to conventional DBS.
The solution
The AlphaDBS neurostimulator, patented and developed by Newronika, was created to provide optimized and personalized control of PD symptoms and represents a new generation of commercially available DBS implantable pulse generator (IPG).
The AlphaDBS neurostimulator delivers adaptive DBS (aDBS) that automatically adjusts the energy delivered to the patient using a validated brain biomarker, in a closed loop configuration. The neurostimulator can also be programmed to conventional DBS mode (with fixed parameters)
The biomarker (a specific signal reflecting neural activity) represents the input variable to the adaptive algorithm implemented by the AlphaDBS system which computes a new stimulation value every second.
This technology, thanks to its recording and closed-loop features, can be defined as a Therapeutic Brain Computer Interface and can be applied to several other conditions where biosignals are disease-specific (e.g. preliminary data have been obtained in Tourette’s Syndrome, Obsessive Compulsive Disorders, Essential Tremor, etc)[1].
The AlphaDBS System with its capability of delivering personalized, “intelligent” adaptive stimulation for PD has been tested in several pilot studies.
The possibility to sense long-term biological signals opens the way to new possibilities to remotely monitor patient state (through validated disease biomarkers) and to conduct remote DBS programming.
In addition, the possibility to record long term brain signals opens the door to an incredible number of future developments in neuromodulation from biomarkers discovery to algorithm generation (also AI based).
The last international study conducted allowed to prove the device safety and effectiveness for CE marking[2]. The AlphaDBS neurostimulator will be tested in a large clinical trial designed to gain FDA approval.
Expected impact
Adaptive DBS will improve the control of PD symptoms, reducing fluctuations, motor (dyskinesias and dystonia) and non-motor side effects (hypomania or impulse control disorders) due to transient summation of the effects of DBS and pharmacological and it is also likely to reduce the development of DBS associated impairment on speech, balance, and gait, and, possibly, cognition. We expect that such improvements will increase the quality of life of PD patients and it will strongly reduce the burden of care on the caregiver, thus improving the quality of life of the caregivers as consequence.
In addition, we expect that the “intelligent” stimulation provided by the AlphaDBS system will increase the productivity of neurologists that manage DBS patients because patient programming can be accomplished in a faster way and patients require less reprogramming.
Eventually such advancements will allow DBS specialists to follow more patients and to expand the DBS market.
External Partners
References
[1] Marceglia S, Rosa M, Servello D, Porta M, Barbieri S, Moro E, Priori A. Adaptive Deep Brain Stimulation (aDBS) for Tourette Syndrome. Brain Sci. 2017 Dec 23;8(1):4. doi: 10.3390/brainsci8010004. PMID: 29295486; PMCID: PMC5789335; Balachandar A, Phokaewvarangkul O, Fasano A. Closed-loop systems for deep brain stimulation to treat neuropsychiatric disorders. Expert Rev Med Devices. 2024 Dec;21(12):1141-1152. doi: 10.1080/17434440.2024.2438309. Epub 2024 Dec 10. PMID: 39644189; Johnson KA, Dosenbach NUF, Gordon EM, Welle CG, Wilkins KB, Bronte-Stewart HM, Voon V, Morishita T, Sakai Y, Merner AR, Lázaro-Muñoz G, Williamson T, Horn A, Gilron R, O’Keeffe J, Gittis AH, Neumann WJ, Little S, Provenza NR, Sheth SA, Fasano A, Holt-Becker AB, Raike RS, Moore L, Pathak YJ, Greene D, Marceglia S, Krinke L, Tan H, Bergman H, Pötter-Nerger M, Sun B, Cabrera LY, McIntyre CC, Harel N, Mayberg HS, Krystal AD, Pouratian N, Starr PA, Foote KD, Okun MS, Wong JK. Proceedings of the 11th Annual Deep Brain Stimulation Think Tank: pushing the forefront of neuromodulation with functional network mapping, biomarkers for adaptive DBS, bioethical dilemmas, AI-guided neuromodulation, and translational advancements. Front Hum Neurosci. 2024 Feb 21;18:1320806. doi: 10.3389/fnhum.2024.1320806. PMID: 38450221; PMCID: PMC10915873; Piña-Fuentes D, Beudel M, Van Zijl JC, Van Egmond ME, Oterdoom DLM, Van Dijk JMC, Tijssen MAJ. Low-frequency oscillation suppression in dystonia: Implications for adaptive deep brain stimulation. Parkinsonism Relat Disord. 2020 Oct;79:105-109. doi: 10.1016/j.parkreldis.2020.08.030. Epub 2020 Aug 23. PMID: 32919097.
[2] Chronic adaptive versus conventional deep brain stimulation in Parkinson’s disease: a blinded randomized pilot trial: Ioannis U. Isaias, Sara Marceglia, Linda Borellini, Enrico Mailland, Filippo Cogiamanian, Sergio Barbieri, Antonella Ampollini, Elena Pirola, Luigi Remore, Laura Caffi, Chiara Palmisano, Claudio Baiata, Salvatore Bonvegna, Luigi Romito, Roberto Eleopra, Vincenzo Levi, Anna Rita Bentivoglio, Carla Piano, Alessandro Izzo, Maurizio Zibetti, Leonardo Lopiano, Michele Lanotte, Tomasz Mandat, Filippo Tamma, Mattia Arlotti, Costanza Conti, Lorenzo Rossi, Guglielmo Foffani, Andres Lozano, Elena Moro, Jens Volkmann, Marco Locatelli, Alberto Priori
medRxiv 2025.02.20.25322374; doi: https://doi.org/10.1101/2025.02.20.25322374; Marceglia S, Conti C, Svanidze O, Foffani G, Lozano AM, Moro E, Volkmann J, Arlotti M, Rossi L, Priori A. Double-blind cross-over pilot trial protocol to evaluate the safety and preliminary efficacy of long-term adaptive deep brain stimulation in patients with Parkinson’s disease. BMJ Open. 2022 Jan 3;12(1):e049955. doi: 10.1136/bmjopen-2021-049955. PMID: 34980610; PMCID: PMC8724732.