MDS 2026 — Huntington's Disease Sessions

The Movement Disorder Society (MDS) International Congress 2026 represents a critical venue for advancing Huntington's disease (HD) research and clinical care. Held in Seoul, Korea, MDS 2026 will feature dedicated sessions addressing the latest advances in understanding, treating, and ultimately preventing this devastating neurodegenerative disorder[@mds].

Overview

Huntington's disease is an autosomal dominant neurodegenerative disorder caused by CAG trinucleotide repeat expansion in the HTT gene, which encodes the huntingtin protein. The mutation leads to progressive degeneration of striatal and cortical neurons, manifesting as a triad of motor, cognitive, and psychiatric symptoms that inexorably worsen over 15-25 years[@bates2015].

The MDS 2026 congress, with its theme of "Understanding Aging in Movement Disorders," provides a particularly relevant context for HD research, given the interplay between the aging process and disease progression. The Congress will feature:

• Gene therapy and huntingtin-lowering approaches
• Disease-modifying therapy updates
• Clinical trial design innovations
• Biomarker development
• Symptomatic treatment advances
• Patient-centered care models

Pathway / Mechanism Diagram

The Movement Disorder Society (MDS) International Congress 2026 represents a critical venue for advancing Huntington's disease (HD) research and clinical care. Held in Seoul, Korea, MDS 2026 will feature dedicated sessions addressing the latest advances in understanding, treating, and ultimately preventing this devastating neurodegenerative disorder[@mds].

Overview

Huntington's disease is an autosomal dominant neurodegenerative disorder caused by CAG trinucleotide repeat expansion in the HTT gene, which encodes the huntingtin protein. The mutation leads to progressive degeneration of striatal and cortical neurons, manifesting as a triad of motor, cognitive, and psychiatric symptoms that inexorably worsen over 15-25 years[@bates2015].

The MDS 2026 congress, with its theme of "Understanding Aging in Movement Disorders," provides a particularly relevant context for HD research, given the interplay between the aging process and disease progression. The Congress will feature:

• Gene therapy and huntingtin-lowering approaches
• Disease-modifying therapy updates
• Clinical trial design innovations
• Biomarker development
• Symptomatic treatment advances
• Patient-centered care models

Pathway / Mechanism Diagram

Congress Details

| Item | Details |
|------|---------|
| Dates | October 4-8, 2026 |
| Location | Seoul, Korea — COEX Convention and Exhibition Center |
| Organizer | Movement Disorder Society |
| Website | [www.mdscongress.org](https://www.mdscongress.org) |
| Theme | Understanding Aging in Movement Disorders |

Gene Therapy Advances

The field of HD gene therapy has made remarkable progress, with multiple modalities advancing toward clinical application:

RNA-Targeting CRISPR Systems

Novel CRISPR/CasRx approaches have demonstrated significant reduction of HTT mRNA levels in HD models. These RNA-targeting systems offer advantages over DNA-editing approaches:

• Allele-selective silencing: Targeting mutant HTT while preserving wild-type expression
• Non-permanent modification: Reversible effects compared to permanent DNA changes
• Reduced off-target effects: Improved specificity compared to earlier CRISPR systems[@roso2023]

Antisense Oligonucleotides (ASOs)

ASOs remain the most advanced gene-silencing approach in clinical development:

Tominersen (RG6042)

• Phase 3 GENERATION HD1 trial: First large-scale ASO trial in HD
• Results informed understanding of target engagement and clinical outcomes
• Lessons learned: Biomarker-guided dosing, early intervention timing

• Multiple ASOs targeting different HTT sequences in development
• Novel chemistries improving delivery and efficacy
• Combination approaches with other therapeutic modalities[@leavitt2020][@mendel2023]

Gene Editing Technologies

Zinc Finger Nucleases (ZFNs)

• Engineered nucleases enabling precise HTT modification
• In vivo delivery approaches showing promise in preclinical models
• First-in-human trials anticipated[@roach2024]

• Single-nucleotide corrections without double-strand breaks
• Potential for allele-specific editing in patients with specific mutations
• Delivery challenges being addressed through AAV and lipid nanoparticle approaches[@kim2024]

• More versatile than base editing, enabling insertions and deletions
• Being optimized for neurological disease applications

Disease-Modifying Therapies

Multiple approaches aim to slow or halt HD progression:

Mutant Huntingtin-Targeting Drugs

Aggregation Modulators

• Small molecules preventing mHTT aggregation
• Autophagy enhancers promoting mHTT clearance
• Proteostasis modulators restoring cellular clearance mechanisms

• Kinase inhibitors affecting phosphorylation
• Acetyltransferase modulators
• SUMOylation pathway modifiers

Neuroprotective Strategies

Mitochondrial Protectants

• CoQ10 and analogues: Antioxidant and electron transport chain support
• Creatine: Energy metabolism support
• PGC-1α modulators: Mitochondrial biogenesis promoters[@hughes2024]

• NMDA receptor antagonists
• AMPA receptor modulators
• Metabolic enhancers reducing excitotoxic vulnerability

• Microglial activation modulators
• Complement system inhibitors
• T cell-targeted interventions[@stringer2023]

Cell-Based Therapies

Stem Cell Approaches

• Embryonic stem cell-derived striatal neurons
• Induced pluripotent stem cell (iPSC) therapies
• Gene-corrected autologous cell approaches
• Encapsulated cell devices for trophic factor delivery[@gonzalez2024]

Clinical Trial Updates

Phase 3 Trial Lessons

The halted trials of 2021 provided critical insights:

Key Learnings

• Early intervention may be essential before substantial neuronal loss
• Biomarker endpoints more sensitive than clinical measures
• Population selection matters: younger patients with less advanced disease
• Genetic stratification may identify optimal responders

• Platform trials enabling efficient testing of multiple interventions
• Adaptive designs allowing mid-course modifications
• Premanifest and early-manifest cohorts
• Enrichment strategies using genetic and biomarker markers[@landles2020]

Biomarker Development

Fluid Biomarkers

• Neurofilament light chain (NfL): Correlation with disease progression
• Tau and p-tau: Emerging markers with cross-disease relevance
• Mutant huntingtin: Quantification in CSF and plasma
• N-terminal huntingtin fragments: Disease state markers

• Volumetric MRI: Striatal and cortical atrophy rates
• Diffusion tensor imaging: White matter integrity
• PET tracers: Mutant huntingtin aggregation imaging
• Functional connectivity: Network-level changes

• Continuous movement monitoring
• Speech and voice analysis
• Oculomotor assessments
• Cognitive testing platforms[@fischer2022][@schultz2022]

Natural History Studies

Long-term observational studies are informing clinical trial design:

• ENROLL-HD: Largest HD natural history study
• PREDICT-HD: Premanifest progression markers
• TRACK-HD: Multimarker disease progression characterization
• Registry: European HD research platform

Symptomatic Treatments

Motor Symptom Management

Chorea Treatments

• Tetrabenazine: First FDA-approved drug for HD chorea
• Deutetrabenazine: Deuterated tetrabenazine with improved tolerability
• Valbenazine: Novel VMAT2 inhibitor with once-daily dosing
• Comparative efficacy and safety data informing treatment choices[@mcgowan2023][@wheelock2023]

• dystonia management
• bradykinesia and rigidity treatment
• gait and balance interventions
• swallowing and speech difficulties

Neuropsychiatric Approaches

Mood Disorders

• Depression: SSRIs, SNRIs, and novel agents
• Anxiety: Integrated pharmacological and behavioral approaches
• Irritability and aggression: Mood stabilizers and behavioral interventions

• Cholinergic enhancement strategies
• Executive function training
• Compensatory strategies and environmental modifications

• Psychosis: Atypical antipsychotics
• Obsessive-compulsive behaviors: SSRIs and behavioral therapy
• Apathy: Dopaminergic and non-dopaminergic approaches[@kumar2024]

Rehabilitation Strategies

• Physical therapy: Exercise programs, gait training
• Occupational therapy: Adaptive equipment, home modifications
• Speech therapy: Communication and swallowing interventions
• Nutritional support: Weight maintenance, dietary planning
• Psychological support: Patients and families

Molecular Mechanisms Sessions

Huntingtontin Protein Aggregation

The pathological aggregation of mutant huntingtin protein represents a central therapeutic target:

• Aggregation kinetics: Nucleation and growth of aggregates
• Toxic species identification: Soluble oligomers vs. insoluble aggregates
• Cellular clearance pathways: Autophagy, proteasome, unfolded protein response
• Propagation mechanisms: Cell-to-cell transmission

CAG Repeat Instability

The CAG repeat tract shows dynamic behavior influencing disease:

• Somatic instability: Tissue-specific expansion patterns
• Intergenerational transmission: Anticipation effects
• Modifiers of repeat stability: Genetic and environmental factors
• Therapeutic implications: Targeting repeat instability[@day2023]

Transcriptional Dysregulation

Mutant huntingtin disrupts normal gene expression patterns:

• Direct binding: HTT interactions with transcription factors
• Chromatin remodeling: Epigenetic alterations
• RNA processing: Splicing and transport abnormalities
• Nuclear import disruption: Altered nucleocytoplasmic transport[@schulte2024]

Mitochondrial Dysfunction

Energy metabolism impairment is a key disease mechanism:

• Complex I deficiency: Electron transport chain abnormalities
• Calcium handling: Mitochondrial calcium dysregulation
• PGC-1α dysfunction: Mitochondrial biogenesis impairment
• Regional vulnerability: Striatal neuron susceptibility[@hughes2024]

Therapeutic Targets Sessions

mHTT Clearance Pathways

Multiple approaches to enhance mutant huntingtin clearance:

• Autophagy induction: mTOR-independent pathways
• Proteasome enhancement: UPS modulation
• Extracellular clearance: Antibody-based approaches
• Aggregated protein removal: Disaggregation strategies

Neuroinflammation in HD

The contribution of neuroinflammation to disease progression:

• Microglial activation: Chronically elevated in HD
• Complement system: C1q and membrane attack complex
• T cell infiltration: Adaptive immune involvement
• Therapeutic targeting: Anti-inflammatory approaches

Synaptic Dysfunction

Early deficits in synaptic function:

• Excitatory synapse loss: Corticostriatal connections
• Spine morphology changes: Structural alterations
• Neurotransmitter dysregulation: Glutamate and GABA
• Synaptic plasticity impairment: Learning and memory deficits

Autophagy Modulation

Enhancing cellular clearance:

• mTOR-independent pathways: Trehalose, rapamycin analogs
• TFEB activation: Transcriptional regulation of autophagy
• Lysosomal function: Enhancing acidification and function
• Chaperone-mediated autophagy: Targeting specific proteins

Related Pages

• [MDS 2026](/events/mds-2026) — Main congress page
• [MDS 2026 — Parkinson's Disease Sessions](/events/mds-2026-parkinsons-sessions)
• [Huntington's Disease](/diseases/huntingtons) — Comprehensive HD overview
• [HTT Gene](/genes/htt) — Huntingtin gene
• [Huntingtin Protein](/proteins/huntingtin) — HTT protein
• [Huntingtin Aggregation](/mechanisms/huntingtin-aggregation)
• [CAG Repeat Instability](/mechanisms/cag-repeat-instability)
• [Transcriptional Dysregulation in Huntington's](/mechanisms/transcriptional-dysregulation-huntingtons)
• [Mitochondrial Dysfunction in Neurodegeneration](/mechanisms/mitochondrial-dysfunction-neurodegeneration)
• [Gene Therapy for Huntington's](/therapeutics/huntingtons-gene-therapy)
• [Antisense Oligonucleotides for HD](/therapeutics/huntingtons-aso-therapy)
• [Clinical Trials in Huntington's Disease](/clinical-trials)

See Also

• [NeuroWiki Home](/home)
• [Movement Disorders Index](/events/conference-index)

External Links

• [MDS Congress](https://www.mdscongress.org)
• [Huntington's Disease Society of America](https://hdsa.org)
• [CHDI Foundation](https://chdifoundation.org)
• [European Huntington Association](https://eurohuntington.org)

References