Four-Layer CNS Biomarker Stratification (Exposure → Target Engagement → Pathway → Clinical) Explains Repeated Late-Stage CNS Trial Failures

Late-stage CNS drug trials frequently fail at the target-engagement-to-pathway-to-clinical transitions; case studies in Huntington disease (tominersen) and Parkinson disease (LRRK2 inhibitor LUMA) illustrate the problem, and improved biomarker stratification is now standard metho

Type

evidence-claim

Domain

h10_altered_intercellular_communication

Grade

A

License

CC BY-NC 4.0

card_id

L-017

hallmarks

h10_altered_intercellular_communication

cluster

methodology

primary_disease_area

alzheimers,parkinsons,huntingtons

evidence_tier

A

evidence_anchor_count

6

intake_round

R23

intake_date

2026-05-26

related_experts

related_biomarkers

related_interventions

related_trials

NCT03761849,NCT05348785

collection_pages

/research/methodology/cns-biomarker-stratification,/research/cases/late-stage-cns-failures

LongProof Longevity Dynamic · LIGHT HOPE / x1000.ai · longevity.x1000.ai · 2026 · source

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