Dates: March 17-21, 2026
Location: Copenhagen, Denmark
Organizer: Kenes Group
Gene therapy emerged as a rapidly evolving area at AD/PD 2026, with multiple programs advancing through clinical development. The conference showcased advances in viral vector delivery, gene silencing technologies, and novel approaches targeting both monogenic and polygenic forms of neurodegenerative diseases.
¶ Vectors and Serotypes
Advances in AAV vector development were a major focus:
- Novel Serotypes: Next-generation AAV variants with improved CNS tropism
- Cross-Blood-Brain-Barrier: Vectors with enhanced BBB penetration
- Targeting Specific Cell Types: Astrocyte and neuron-specific promoters
- Manufacturing Advances: Scalable production methods for clinical supply
- AAV2-GAD - Neurologix: Glutamic acid decarboxylase gene therapy for motor symptoms
- VY-AADC02 - Voyager: Optimized aromatic L-amino acid decarboxylase delivery
- AAV2-AADC - Meir Pharma: Ongoing clinical validation
- BDNF Delivery: Brain-derived neurotrophic factor gene therapy
- APOE4 Modulation: Gene therapy approaches to modify APOE4 risk
- Anti-Amyloid Gene Therapy: Novel approaches to continuous amyloid reduction
ASO technology continues to advance:
- SNCA Targeting: ASOs for alpha-synuclein reduction in PD
- GBA Carriers: ASOs for glucocerebrosidase modulation in GBA-associated PD
- MAPT Targeting: Tau-targeting ASOs in AD
- Stereotactic Delivery: Direct brain delivery approaches
- Viral-Mediated RNAi: AAV-delivered short hairpin RNAs
- Allele-Specific Silencing: Targeting mutant alleles in genetic forms
- Non-Viral Delivery: Lipid nanoparticle approaches for siRNA delivery
¶ CRISPR and Genome Editing
Base editing technologies were highlighted as next-generation approaches:
- Prime Editing: More precise genetic modifications
- Allele-Specific Editing: Targeting disease-causing mutations
- Epigenetic Modulation: CRISPR approaches to gene expression regulation
- AAV-CRISPR: Direct delivery of CRISPR components to CNS
- Non-Viral Vectors: Novel delivery methods for genome editing
- Safety Considerations: Off-target effects and immunogenicity
- GDNF - Virin: Glial cell line-derived neurotrophic factor gene therapy
- Neurturin: AAV-delivered neurturin for PD
- BDNF Variants: Engineered brain-derived neurotrophic factors
- Multi-Gene Therapy: Simultaneous delivery of multiple therapeutic genes
- Gene Therapy + Small Molecule: Combined delivery and pharmacological approaches
- Kinase Domain Mutants: Gene therapy for specific LRRK2 mutations
- Gene Replacement: Wild-type LRRK2 delivery for loss-of-function variants
- Enzyme Enhancement: Gene therapy for glucocerebrosidase
- Substrate Reduction: Combined approaches for GBA-associated PD
- Alpha-Synuclein Reduction: Multiple approaches to lower SNCA expression
- Aggregation Modifiers: Genes affecting alpha-synuclein aggregation
¶ APP and Amyloid
- APP Modulation: Gene therapy approaches to amyloid production
- BACE Targeting: Genetic approaches to beta-secretase modulation
- APOE4 Conversion: Gene therapy to modify APOE4 to APOE3
- ** APOE2 Delivery**: Protective APOE2 for APOE4 carriers
- Multiple Phase 1/2 trials showing safety and preliminary efficacy
- Long-term follow-up data from early gene therapy trials
- Biomarker-based patient selection for genetic subpopulations
- Accelerated Approval: Gene therapy regulatory pathways for neurodegenerative diseases
- Combination Therapy Guidance: Regulatory frameworks for gene therapy combinations
- Manufacturing Standards: CMC requirements for gene therapy products
- Self-complementary AAV vectors for enhanced expression
- Dual-promoter systems for cell-type specificity
- Regulatable expression systems
- Intranasal delivery for non-invasive CNS targeting
- Systemic delivery with targeted CNS uptake
- CSF administration for widespread CNS distribution
- AAV technology maturing — Multiple clinical programs showing safety signals
- Genetic stratification increasing — More trials targeting specific genetic subtypes
- Delivery advances — Novel vectors with improved brain penetration
- Gene silencing progressing — ASO and siRNA approaches entering CNS trials
- Combination strategies — Gene therapy + pharmacological combinations emerging