Objective: 1. To assess brain network level dysfunction of Huntington disease (HD). 2.  To evaluate the effectiveness of 2-week home-based chronic non-invasive transcranial brain stimulation (NIBS) in HD.

Background: Therapeutic trials in HD have failed to show any promising results with pharmacotherapy. Recent failure of trials with ASO has created a major setback in HD research [1]. Thus, there is still a significant unmet treatment need. Current studies have shown multilevel network dysfunction in neurodegenerative disorders beyond the basal ganglia. Targeting network level dysfunction by NIBS is a novel therapeutic option in these disorders [2]. In this pilot study, we are investigating the efficacy of 2-week home-based non-invasive stimulation by tPCS in patients with HD.

Method: Fifteen patients with HD will be assessed for the following parameters: Upper limb movements using KinArm, gait using ZenoWalkway and PKMAS software, quantitative EEG (qEEG), Unified Huntington disease rating scale (UHDRS) and Beck Depression Inventory (BDI). tPCS is delivered by placing anode over the scalp on the dysfunctional brain region, as evidenced by qEEG, and cathode is placed over the mid-thoracic spine. Each patient receives active and sham stimulation with a 1-month gap in between, in a randomized blinded fashion. Patients are assessed initially before the stimulation and then after receiving 2-week home-based stimulation (20 min per day). Upon completion of recruitment, analysis will compare pre and post stimulation data in network level entropy scores, gait features, Kin Arm and clinical scores.

Results: The study is actively recruiting. So far, we have recruited 10 patients, 4 of them finished the study. Patients are not having difficulty to set up the home-based stimulation. All patients well tolerated chronic tPCS and have not reported any side effects. Patient compliance is good and we don’t have any dropouts.

Conclusion: This is an ongoing study. Home-based tPCS is a well-tolerated, cost effective, non-invasive brain stimulation with good compliance. Localization of network dysfunction by qEEG make it feasible to deliver tPCS precisely. Clinical rating scales for motor symptoms and depression, along with upper limb kinematic assessment and gait study are helping in characterization of HD patients and monitoring the therapeutic response to chronic tPCS.

References: 1. Tabrizi SJ, Leavitt BR, Landwehrmeyer GB, et al. Targeting Huntingtin Expression in Patients with Huntington’s Disease. N Engl J Med. 2019;380(24):2307-2316. doi:10.1056/NEJMoa190090.
2. Ganguly J, Murgai A, Sharma S, Aur D, Jog M. Non-invasive Transcranial Electrical Stimulation in Movement Disorders. Front Neurosci. 2020 Jun 5;14:522. doi: 10.3389/fnins.2020.00522.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-randomized-sham-controlled-crossover-trial-on-transcranial-pulsed-current-stimulation-tpcs-in-huntington-disease/