MedCentralAAN Annual Meeting 2026 Research Recap

The American Academy of Neurology’s 2026 annual meeting featured nine late-breaking trials spanning rare neurodegenerative disease to autoimmune syndromes. Results ranged from positive primary endpoints (levacetylleucine, crisugabalin, miv-cel CAR T) to high-profile negative findings (latozinemab in FTD-GRN) and observational safety signals (GLP-1 analogues and cognitive impairment).

Clinical Considerations

• Levacetylleucine met the primary SARA endpoint in ataxia-telangiectasia (treatment effect −1.88; P < 0.001) across 73 participants aged 4 to 50, with no treatment-emergent events above 10%.
• Atogepant sustained migraine reduction over 156 weeks, with mean MMD change of −9.2 at study end and no new safety signals; 83.2% AE rate reflected predominantly non-serious events.
• Latozinemab raised plasma progranulin 165% in FTD-GRN but showed no clinical or biomarker benefit on CDR-FTLD or NfL over 96 weeks, illustrating that target engagement does not guarantee disease modification.
• A TriNetX cohort of 512,037 patients with type 2 diabetes found GLP-1 analogue use associated with HR 2.74 for cognitive impairment but HR 0.68 for mortality, with no significant composite difference — a competing-risk pattern requiring careful interpretation.
• Crisugabalin reduced central neuropathic pain in 408 patients with spinal cord injury or post-stroke pain (ADPS −2.39 vs −1.15; P < 0.0001), with onset by week 1.
• Miv-cel CAR T-cell therapy met the primary T25FW endpoint in 26 patients with refractory stiff person syndrome (45.6% improvement; P = 0.0003); CRS occurred in 92.3% (all grade 1-2).
• TRAILBLAZER-ALZ 2 extension data showed early-start donanemab continuers had higher baseline amyloid (122.0 vs 94.8 CL) and APOE4 rates (80.3% vs 63.4%), with higher ARIA-E (24.2%) and ARIA-H (37.6%) but comparable 3-year clinical outcomes.
• Azetukalner (X-TOLE2) and fenebrutinib (FENhance 1/2) completed enrollment in treatment-resistant focal seizures and relapsing MS respectively, but efficacy and safety results were not reported at AAN.

Practice Applications

• Interpret the GLP-1 cognitive signal cautiously: observational, residual confounding likely, with competing mortality benefit complicating risk-benefit framing.
• Recognize latozinemab’s negative result as informing the broader question of whether progranulin restoration alone is sufficient in FTD-GRN.
• Monitor for full X-TOLE2 and FENhance readouts before drawing conclusions on azetukalner or fenebrutinib.
• Consider age stratification when discussing GLP-1 use in older adults with type 2 diabetes; the 80+ subgroup showed the strongest cognitive signal.
• Avoid extrapolating CAR T-cell results in SPS beyond the refractory population studied; durability data remain limited at 6.5-month median follow-up.