MDS 2026 — Emerging Therapeutics in Parkinson's Disease

MDS 2026 Parkinsons Emerging Therapeutics

Congress: Movement Disorder Society (MDS) International Congress 2026 Dates: October 4-8, 2026 Location: Seoul, Korea — COEX Convention and Exhibition Center Theme: Understanding Aging in Movement Disorders

Overview

MDS 2026 Parkinsons Emerging Therapeutics

Congress: Movement Disorder Society (MDS) International Congress 2026 Dates: October 4-8, 2026 Location: Seoul, Korea — COEX Convention and Exhibition Center Theme: Understanding Aging in Movement Disorders

Overview

The development of disease-modifying therapies for Parkinson's disease (PD) remains one of the most important goals in movement disorder research. While current treatments effectively manage symptoms, they do not slow or halt disease progression. MDS 2026 will showcase the latest advances in disease-modifying approaches, including alpha-synuclein-targeted therapies, gene therapies, cell-based treatments, and novel neuroprotective strategies["@lang2006"][@stocchi2015].

Alpha-Synuclein-Targeted Therapies

Immunotherapies

Active Immunization

• PD01A (Affiris): Peptide vaccine targeting aggregated α-synuclein
• Phase 1: Safe and well-tolerated
• Phase 2: Demonstrated antibody response, trial ongoing
• ACI-35 (AC Immune/Lilly): Liposome-based vaccine with phosphorylated α-synuclein
• Induces antibodies targeting pathological phosphorylated α-synuclein

Passive Immunization

• Prasinezumab (RO7046015/PRX002): Monoclonal antibody against aggregated α-synuclein
• Phase 2 (PASADENA): Reduced progression of motor symptoms
• Phase 2b (PADOVA): Ongoing in patients with motor fluctuations
• Cinpanemab (BIIB054): Monoclonal antibody targeting α-synuclein
• Phase 2 (SPARK): Primary endpoint not met, subgroup analysis encouraging
• AL-108 (Alzheon): Oligomer modulator targeting α-synuclein aggregation

Small Molecule Aggregation Inhibitors

• Mannitol: Sugar alcohol reducing α-synuclein aggregation (in use for other purposes)
• Anle138b: Oligomer modulator showing promise in preclinical models
• SynuClean-D: Compound preventing α-synuclein fibrillation
• EPI-589: Redoxactive small molecule targeting neuroinflammation and α-syn

Gene Therapies

AAV-Based Gene Delivery

Aromatic L-Amino Acid Decarboxylase (AADC)

• VY-AADC (Voyager Therapeutics): AAV2 vector delivering AADC gene to striatum
• Results: Improved motor function, reduced levodopa requirements
• Phase 1b: Sustained benefits for 4+ years
• Phase 2: SPARK trial completed

Glutamic Acid Decarboxylase (GAD)

• AAV-GAD (Neurologix): Gene therapy for GABA production
• Results: Improved motor scores in pilot study

Neurotrophic Factors

• AAV-NTN (Cerevel/Roche): Neurturin delivery for neuroprotection
• Results: Mixed; REGN0040 ongoing

Gene Silencing Approaches

• ASOs (Antisense Oligonucleotides): Targeting SNCA gene expression
• IONIS-SYNC Rx (Ionis/Biogen): Phase 1/2a completed
• WVE-003 (Wave Life Sciences): Allele-selective targeting of mutant SNCA

CRISPR-Based Approaches

• Gene Editing: Targeting SNCA, LRRK2, GBA mutations
• Prime Editing: Precise DNA corrections
• Base Editing: Single nucleotide modifications

Cell-Based Therapies

Dopaminergic Cell Replacement

Embryonic Stem Cell (ESC) Derivatives

• ESC-derived dopamine neurons:
• Clinical trials ongoing in Japan (Kyoto University)
• Showing promising survival and function
• Allogeneic vs. Autologous: Current trials use allogeneic cells

Induced Pluripotent Stem Cell (iPSC) Therapy

• Autologous iPSC-derived dopamine neurons:
• Japan: First human trial initiated (Kobe University)
• Advantages: No immunosuppression required
• Challenges: Cost, manufacturing scale-up
• Allogeneic iPSC banks: HLA-matched cell lines in development

Stromal Cell Therapies

• Mesenchymal stem cells (MSCs): Neuroprotective and immunomodulatory effects
• Multiple trials in various phases
• Delivery: Intravenous, intra-arterial, intrathecal

Tissue Engineering

• Cell encapsulated in alginate beads: Controlled neurot factor release
• 3D bioprinting: Creating structured neural tissue constructs

LRRK2-Targeted Therapies

LRRK2 Inhibitors

• DNL151 (Denali Therapeutics/Biogen): LRRK2 kinase inhibitor
• Phase 1: Safe, target engagement demonstrated
• Phase 2: Ongoing in PD patients
• BIIB122 (Biogen): LRRK2 inhibitor, acquired from Denali
• Phase 2b: Testing in early PD
• DNL758 (Denali): CNS-penetrant LRRK2 inhibitor

LRRK2 Modulators

• Stereotyped ASOs: Targeting LRRK2 mRNA for allele-specific silencing

GBA-Targeted Approaches

GCase Modulation

• Ambroxol: GCase chaperone
• Phase 2: Showing increased GCase activity in CSF
• Potential for combination with other approaches
• L渠-483 (IDCP): GCase activator in development

Gene Therapy

• AAV-GBAs1: Gene delivery of functional GCase

Anti-Neuroinflammatory Therapies

Microglial Modulation

• TREM2-targeting antibodies: Controlling microglial activation
• CSF1R inhibitors: Targeting colony-stimulating factor 1 receptor
• Minocycline: Broad anti-inflammatory effects (clinical trials mixed)

Neuroimmune Modulation

• NLRP3 inhibitors: Blocking inflammasome activation
• IL-1β antagonists: Canakinumab being explored

Mitochondrial and Bioenergetic Therapies

Mitochondrial Biogenesis

• CoQ10: Electron transport chain support
• Phase 2: Mixed results (QE3 trial negative)
• Subgroup analysis: Earlier patients may benefit
• Mitochondrial toxins: KATs (kinase activators)

Mitophagy Enhancement

• Rapamycin: mTOR inhibition promotes autophagy
• Urolithin A: Mitophagy inducer (showing promise in muscle function)

Other Novel Approaches

GLP-1 Receptor Agonists

• Exenatide: GLP-1 receptor agonist
• Phase 2: Improved motor scores in off-med state
• Phase 3: Exenatide-PD trial underway
• Liraglutide: Similar approach, ongoing trials
• Semaglutide: Once-weekly GLP-1 agonist

Iron Chelation

• Deferoxamine: Reducing iron accumulation in substantia nigra
• Deferasirox: Oral iron chelator in trials

Sigma-1 Receptor Agonists

• Pridopidine: Targeting sigma-1 receptor for neuroprotection

Calcium Channel Blockers

• Isradipine: L-type calcium channel blocker
• Phase 3 (STEADY-PD III): Did not meet primary endpoint

Potassium Channel Openers

• Ipratropium: Kv7 channel activator showing neuroprotective effects

Disease-Modifying Trial Design

Challenges

• Slow disease progression: Requires long trials or sensitive endpoints
• Lack of validated biomarkers: Surrogate endpoints needed
• Heterogeneous patient populations: Different pathogenic subtypes

Innovative Trial Designs

| Design | Description | Advantages |
|--------|-------------|------------|
| Delayed-start | Randomized to treatment vs. placebo, then both to treatment | Measures disease modification |
| Placebo-delay | All patients eventually receive treatment | Ethical advantages |
| Adaptive designs | Sample size re-estimation, arm selection | Efficiency |
| Pre-motor enrollment | Prodromal PD subjects | Earlier intervention |

Outcome Measures

• Clinical: MDS-UPDRS, MoCA, various disability scales
• Biomarker: αSyn-SAA,NfL, neuroimaging
• Digital: Wearable-based measures

Sessions and Presentations

Expected Topics

Related Pages

• [MDS 2026 — Main Congress Page](/events/mds-2026)](/events)
• [MDS 2026 — Parkinson's Disease Sessions](/events/mds-2026-parkinsons-sessions)](/events)
• [Parkinson's Disease](/diseases/parkinsons-disease)](/proteins/parkin)
• [Parkinson's Disease Treatment](/therapeutics/parkinsons-disease-treatment)](/therapeutics)
• [Alpha-Synuclein Protein](/proteins/alpha-synuclein)](/proteins)
• [LRRK2 Gene](/genes/lrrk2)](/genes)
• [GBA Gene](/genes/gba)](/genes)
• [Cell Therapy for Parkinson's](/therapeutics/cell-therapy-parkinsons)](/therapeutics)
• [Gene Therapy for Parkinson's](/therapeutics/gene-therapy-parkinsons)](/therapeutics)
• [MDS 2026 — Clinical Trials](/events/mds-2026-parkinsons-clinical-trials)](/clinical-trials)
• [MDS 2026 — Diagnostics & Biomarkers](/events/mds-2026-parkinsons-diagnostics-biomarkers)

References

External Links

• [MDS Congress 2026](https://www.mdscongress.org)
• [Michael J. Fox Foundation - Therapeutic Pipeline](https://www.michaeljfox.org/)
• [International Parkinson and Movement Disorders Society](https://www.movementdisorders.org/)](/proteins/parkin)
• [ClinicalTrials.gov - Parkinson's Disease](https://clinicaltrials.gov/)