The Movement Disorders Society (MDS) 2026 Congress showcased significant advances in surgical therapies for Parkinson's disease (PD), including updates on deep brain stimulation (DBS) technology, gene therapy approaches, and lesional surgery techniques. This page summarizes the key presentations and clinical evidence from the meeting.
Two major targets remain standard for PD DBS: the subthalamic nucleus (STN) and globus pallidus interna (GPi). New 10-year follow-up data from the landmark trials demonstrate:
- STN-DBS: 55-60% improvement in UPDRS motor scores, 60-70% reduction in levodopa equivalent dose
- GPi-DBS: 45-50% motor improvement, 25-40% medication reduction, superior dyskinesia control
- Cognitive outcomes: GPi target shows less cognitive decline than STN in long-term follow-up
- Speech outcomes: GPi associated with better speech preservation
MDS 2026 Consensus: GPi increasingly preferred for patients with cognitive concerns or speech/gait predominance; STN remains standard for patients requiring maximum medication reduction.
The introduction of segmented (directional) electrodes has improved the therapeutic window by 25-30%:
- Current steering allows precise targeting of motor territory while avoiding side effect zones
- Improved dyskinesia control through ventral contact activation
- Reduced stimulation-induced side effects (speech, gait, mood)
New data from MDS 2026 showed that directional leads enable:
- 40% reduction in stimulation-related speech side effects
- Customized symptom-specific programming
- Better outcomes in challenging anatomies
Closed-loop adaptive DBS systems that respond to neural biomarkers were prominently featured:
Key findings:
- Beta-band (13-35 Hz) oscillations serve as reliable biomarker for motor state
- Adaptive stimulation reduces energy consumption by 40-50% while maintaining efficacy
- Improved nighttime symptom control compared to continuous stimulation
- Machine learning algorithms now enable personalized biomarker detection
Emerging systems:
- Medtronic Percept PC with BrainSense technology
- Boston Scientific Vercise Cartesia with directional sensing
- Abbott Infinity system with directional leads and sensing
The EARLYSTIM trial 5-year extension data confirmed that DBS in early motor complications provides:
- Superior quality of life outcomes versus medical therapy alone
- Reduced progression of motor complications
- No increased cognitive decline compared to medical arm
MDS 2026 recommendation: Consider DBS for patients with motor complications despite optimal medical therapy, regardless of disease duration if functional impairment is significant.
芳香族氨基酸脱羧酶 (AADC) gene therapy continues to show promise:
Clinical outcomes:
- 5-year follow-up data shows sustained motor improvements (40-50% UPDRS reduction)
- Reduced levodopa requirements (50-70% decrease)
- Improved "on" time without dyskinesia
- Safety profile remains favorable with no serious adverse events related to vector
Key programs:
- VY-AADC (Voyager Therapeutics): Received FDA breakthrough therapy designation
- AB-1005 (Aspen Neuroscience): Autologous AADC-expressing cells in development
- BEMDANEPROCEL (Roche/BrainNeuro): Shows promise in Phase 2
GDNF (glial cell line-derived neurotrophic factor) gene therapy represents a neuroprotective approach:
Phase 2 results:
- AAV2-GDNF delivery to putamen showed good tolerability
- biomarker evidence of increased dopamine storage capacity
- Motor improvement trends observed at 2-year follow-up
- Ongoing Phase 2b trials
Mechanism: GDNF promotes survival and function of dopaminergic neurons, potentially slowing disease progression.
Patients with GBA gene mutations represent a priority population for gene therapy:
- GBA gene augmentation: AAV-vector delivery of functional GBA1
- Preclinical data: Shows reduction in alpha-synuclein pathology in GBA models
- Clinical translation: Expected Phase 1 trials in 2026-2027
MRI-guided focused ultrasound has expanded beyond essential tremor to PD:
Unilateral thalamotomy for tremor-dominant PD:
- 60-70% tremor reduction in tremor-dominant PD
- Particularly effective for rest tremor and postural tremor
- Most common side effect: transient dysarthria (15-20%)
- Sustained benefits at 3-year follow-up
VIM versus GPi targeting:
- VIM: Superior for tremor suppression
- GPi: Additional benefit for dyskinesias but less data
Bilateral GPi pallidotomy using focused ultrasound:
MDS 2026 data:
- Significant reduction in dyskinesias (70-80%)
- Moderate improvement in motor scores (30-40%)
- Challenge: bilateral procedures associated with higher adverse event rate
- Single-side pallidotomy plus contralateral thalamotomy emerging as alternative
The subthalamic nucleus as a lesioning target is emerging:
Early results:
- Improvement in motor symptoms similar to DBS effects
- Reduction in medication requirements
- Risk of persistent side effects requires careful patient selection
- Technically challenging due to small target size
| Therapy |
Target |
Invasiveness |
Reversibility |
Best For |
| STN-DBS |
Subthalamic Nucleus |
High |
Yes |
Advanced PD, max medication reduction |
| GPi-DBS |
Globus Pallidus interna |
High |
Yes |
Dyskinesias, cognitive concerns |
| aDBS |
STN/GPi |
High |
Yes |
Variable symptoms, resource optimization |
| FUS Thalamotomy |
VIM thalamus |
Low |
No |
Tremor-dominant, surgery-averse patients |
| FUS Pallidotomy |
GPi |
Low |
No |
Dyskinesia-predominant PD |
| Gene Therapy |
Striatum |
High |
No |
Refractory motor fluctuations |
Factors favoring DBS:
- Clear levodopa response
- Motor fluctuations or dyskinesias
- No significant cognitive impairment
- Good surgical risk
Factors favoring FUS:
- Elderly or poor surgical risk
- Contraindication to implanted hardware
- Tremor-predominant phenotype
- Single symptom target
- Wireless DBS systems: Elimination of subcutaneous cables
- MRI-conditional full-body systems: Safe scanning with implanted devices
- ** rechargeable batteries**: 15-20 year lifespan
- Automated symptom detection from neural signals
- Personalized parameter optimization using AI
- Remote monitoring and adjustment capabilities
- DBS plus gene therapy (sequential or concurrent)
- FUS plus pharmacotherapy
- Cell replacement plus neuromodulation
¶ Clinical Trial Landscape
- NCT06584383: Focused ultrasound subthalamotomy in early PD
- NCT06742450: Constant-current versus voltage-controlled DBS
- NCT07022522: Frequency-specific subthalamic DBS
- NCT07218081: DBS of nucleus basalis for cognition
- Gene therapy for GBA-PD
- Multi-target DBS for axial symptoms
- Closed-loop systems for gait freezing