MDS 2026: Surgical Therapies for Parkinson's Disease

Overview

Overview

The Movement Disorders Society (MDS) 2026 Congress showcased significant advances in surgical therapies for Parkinson's disease (PD), including updates on [deep brain stimulation](/therapeutics/deep-brain-stimulation) (DBS) technology, [gene therapy](/therapeutics/gene-therapy) approaches, and [lesional surgery](/therapeutics/focused-ultrasound-parkinson) techniques. This page summarizes the key presentations and clinical evidence from the meeting.

Deep Brain Stimulation Advances

STN versus GPi: Long-term Outcomes

Two major targets remain standard for PD DBS: the [subthalamic nucleus](/brain-regions/subthalamic-nucleus) (STN) and [globus pallidus interna](/brain-regions/globus-pallidus) (GPi). New 10-year follow-up data from the landmark trials demonstrate[@stn_vs_gpi_2025]:

• 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

Directional Leads

The introduction of segmented (directional) electrodes has improved the therapeutic window by 25-30%[@directional_leads_2025]:

• 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)

• 40% reduction in stimulation-related speech side effects
• Customized symptom-specific programming
• Better outcomes in challenging anatomies

Adaptive DBS

Closed-loop [adaptive DBS](/technologies/adaptive-dbs) systems that respond to neural biomarkers were prominently featured[@adaptive_dbs_trial][@closed_loop_2025]:

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

• Medtronic Percept PC with BrainSense technology
• Boston Scientific Vercise Cartesia with directional sensing
• Abbott Infinity system with directional leads and sensing

Early Intervention DBS

The EARLYSTIM trial 5-year extension data confirmed that DBS in early motor complications provides[@early_dbs_2025]:

• Superior quality of life outcomes versus medical therapy alone
• Reduced progression of motor complications
• No increased cognitive decline compared to medical arm

Gene Therapy Updates

AAV-AADC Therapy

芳香族氨基酸脱羧酶 (AADC) gene therapy continues to show promise[@gene_therapy_aadc_2025]:

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

• 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

AAV-GDNF Therapy

[GDNF (glial cell line-derived neurotrophic factor) gene therapy](/therapeutics/gdnf-therapies) represents a neuroprotective approach[@gdnf_gene_2025]:

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

Gene Therapy for GBA-PD

Patients with [GBA gene](/genes/gba) 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

Lesional Surgery

Focused Ultrasound Thalamotomy

[MRI-guided focused ultrasound](/therapeutics/focused-ultrasound-parkinson) has expanded beyond essential tremor to PD[@focused_ultrasound_2025]:

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: Superior for tremor suppression
• GPi: Additional benefit for dyskinesias but less data

Focused Ultrasound Pallidotomy

[Bilateral GPi pallidotomy](/therapeutics/focused-ultrasound-thalamotomy) 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

Focused Ultrasound Subthalamotomy

The [subthalamic nucleus](/brain-regions/subthalamic-nucleus) as a lesioning target is emerging[@subthalamotomy_2025]:

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

Comparative Effectiveness

Surgical Options Comparison

| 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 |

Patient Selection Factors

Factors favoring DBS:

• Clear levodopa response
• Motor fluctuations or dyskinesias
• No significant cognitive impairment
• Good surgical risk

• Elderly or poor surgical risk
• Contraindication to implanted hardware
• Tremor-predominant phenotype
• Single symptom target

Emerging Technologies at MDS 2026

Next-Generation Devices

Biomarker-Driven Programming

• Automated symptom detection from neural signals
• Personalized parameter optimization using AI
• Remote monitoring and adjustment capabilities

Combined Modality Approaches

• DBS plus gene therapy (sequential or concurrent)
• FUS plus pharmacotherapy
• Cell replacement plus neuromodulation

Clinical Trial Landscape

Active Registration Trials

• 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

Upcoming Trials

• Gene therapy for GBA-PD
• Multi-target DBS for axial symptoms
• Closed-loop systems for gait freezing

See Also

• [Deep Brain Stimulation](/therapeutics/deep-brain-stimulation)
• [Adaptive DBS Technology](/technologies/adaptive-dbs)
• [Focused Ultrasound for Parkinson's Disease](/therapeutics/focused-ultrasound-parkinson)
• [Gene Therapy for Neurodegeneration](/therapeutics/gene-therapy-neurodegeneration)
• [GDNF Therapies](/therapeutics/gdnf-therapies)
• [AADC Gene Therapy](/therapeutics/aadc-gene-therapy)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [MDS 2026 Main Page](/events/mds-2026)

References