AAN 2026 — Multiple Sclerosis

Dates: April 18-22, 2026 Location: McCormick Place, Chicago, Illinois Track: Neuroimmunology and Multiple Sclerosis

Overview

Multiple sclerosis (MS) continues to be a major focus at AAN, with the 2026 meeting covering the latest advances in disease-modifying therapies, progressive MS treatment, remyelination strategies, and biomarker-guided monitoring. The field has undergone a dramatic transformation over the past decade with the approval of numerous highly effective therapies, and AAN 2026 will focus on optimizing treatment selection, managing treatment transitions, and addressing the remaining unmet needs in progressive MS and neuroprotection.

Pathway / Mechanism Diagram

graph TD
    A["Genetic + Environmental Triggers"] --> B["Autoreactive T-Cell Activation"]
    B --> C["BBB Breach and CNS Infiltration"]
    C --> D["Th1/Th17 Attack on Myelin"]
    C --> E["B-Cell and Antibody Damage"]
    D --> F["Demyelination"]
    E --> F
    F --> G["Axonal Exposure"]
    G --> H["Conduction Block"]
    H --> I["Relapsing Symptoms"]
    F --> J["Remyelination Attempt (OPC)"]
    J --> K["Partial Recovery"]
    G --> L["Progressive Axonal Degeneration"]
    L --> M["Neuronal Loss"]
    M --> N["Irreversible Disability (SPMS)"]
    D --> O["Chronic Neuroinflammation"]
    O --> L
    style F fill:#ef5350,color:#e0e0e0
    style N fill:#ef5350,color:#e0e0e0
    style K fill:#1b5e20,color:#e0e0e0

Disease-Modifying Therapies

B-Cell Targeted Therapies

B-cell depletion remains the most effective approach for relapsing MS, with several key updates expected^{1B-cell therapies in multiple sclerosis: 2024 update2024 · Neurology · PMID 38381818Open reference}:

• Ocrelizumab (Ocrevus): Extended follow-up data from the Phase 3 trials, real-world effectiveness data from international registries (MSBase, CMSC), and safety surveillance for hypogammaglobulinemia

• Ofatumumab (Kesimpta): New data on very early treatment initiation in clinically isolated syndrome (CIS), combination strategies, and long-term B-cell reconstitution

• Ublituximab: Real-world experience data and head-to-head comparisons with other anti-CD20 therapies

High-Efficacy Oral and Infusion Therapies

• Natalizumab (Tysabri): Risk stratification updates for progressive multifocal leukoencephalopathy (PML), especially regarding JC virus antibody titers and treatment duration

• Fingolimod (Gilenya): Cardiac monitoring protocols updated, use in pediatric MS, and post-marketing safety data

• Siponimod (Mayzent): Data in secondary progressive MS with active disease

• Cladribine (Mavenclad): Long-term safety and efficacy, retreatment protocols

Emerging Oral Agents

• Evobrutinib (BTK inhibitor): Phase 3 results expected

• Fenebrutinib (BTK inhibitor): Updated Phase 3 data

• Atacicept (BAFF/APRIL inhibitor): Phase 2 results in MS

Progressive MS

Progressive MS remains the most challenging frontier, with several promising approaches in late-stage development^{2Progressive MS: emerging treatment targets2024 · Lancet Neurol · PMID 38634567Open reference}:

Anti-LCMV Approaches

• Sonepcizumab (anti-LINGO): Updates on remyelination efficacy

• Opicinumab: Biomarker predictors of response

Neuroprotection

• SLC9A9A (NHE1) modulators: Preclinical data supporting neuroprotection

• Vitamin D supplementation trials: Mechanistic studies

• Sodium monomethyl fumarate: Neuroprotective mechanisms

Symptom Management Trials

• Siponimod in SPMS: Post-hoc analyses of subgroups most likely to benefit

• Simvastatin in secondary progressive MS: Negative Phase 3 results and mechanistic lessons

Biomarkers

Neurofilament Light Chain (NfL)

NfL has emerged as a critical biomarker for MS disease activity and treatment response^{3Neurofilament light chain as biomarker in MS2024 · Ann Neurol · PMID 38205974Open reference}:

• Serum NfL as a treatment response marker for anti-CD20 therapies

• Baseline NfL as a prognostic factor for conversion from CIS to MS

• NfL trajectories in pregnant MS patients

• Comparison of NfL across different assay platforms (Simoa, Elecsys)

• Normalization of NfL with effective treatment as a therapeutic goal

Other Biomarkers

• Glial fibrillary acidic protein (GFAP): Specific for astroglial injury, useful in progressive MS

• Chitinase-3-like protein 1 (CHI3L1/YKL-40): Astrocyte activation marker

• OCT (optic coherence tomography): Retinal nerve fiber layer as a proxy for neurodegeneration

• MRI metrics: Slowly expanding lesions (SELs) as a progressive MS marker

Remyelination and Repair

The regeneration of myelin sheaths represents a major therapeutic frontier^{4Remyelination strategies in MS2023 · Brain · PMID 36912089Open reference}:

Small Molecule Remyelinating Agents

• Clemastine: Muscarinic antagonist promoting oligodendrocyte differentiation, with human data from ReBUILD trial

• GSK239512 (H3 receptor agonist): Ongoing clinical trials

• Biotin (Qizenday): Approved in Europe for progressive MS, US data awaited

Cell-Based Approaches

• Oligodendrocyte progenitor cell (OPC) transplantation: Phase 1 trials

• Mesenchymal stem cell-derived extracellular vesicles: Phase 2 data

Combination Strategies

• Anti-inflammatory therapy + remyelination agents

• Physical therapy and targeted rehabilitation to enhance remyelination

Pediatric MS

• DMT selection in pediatric-onset MS

• Adolescent transition to adult care

• Vaccinations and immune responses during DMT

• School and social support strategies

Specific Sessions and Symposia

Late-Breaking Science

AAN 2026 will feature late-breaking results from:

• Phase 3 trials of BTK inhibitors in relapsing MS

• Long-term extension data for recently approved therapies

• Real-world evidence studies from large MS registries

Hands-On Workshops

• MRI interpretation for MS diagnosis and monitoring

• OCT practical training for neuro-ophthalmic assessment

• Neurological examination workshop for MS trainees

Meet-the-Expert Sessions

• Treatment algorithms in highly active MS

• Managing breakthrough disease on DMTs

• Reproductive health and family planning in MS

Key Opinion Leaders

Expected speakers include leading MS researchers from Cleveland Clinic, UCSF, Johns Hopkins, Brigham and Women’s, University of Cambridge (UK), Karolinska Institutet (Sweden), and VUmc Amsterdam.

Therapeutic Pipeline

See Also

• Multiple Sclerosis

• AAN 2026 — Main conference page

• AAN 2026 Alzheimer’s Disease

• AAN 2026 Parkinson’s Disease

• AAN 2026 Dementia

• AAN 2026 ALS

• Alpha-Synuclein

• Myelin Basic Protein

• Oligodendrocyte