Progranulin Replacement Therapy for FTD — Vector Development and Validation

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Progranulin Replacement Therapy for FTD — Vector Development and Validation

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experiment Created: 2026-04-02T10:01:41 By: crosslink-v2 Quality: 67% ✓ SciDEX ID: experiment-exp-wiki-experiments-progranu

🧫 Experiment Protocol Clinicalproposed

SUMMARY

# Progranulin Replacement Therapy for FTD — Vector Development and Validation ## Background and Rationale This clinical trial focuses on developing and validating progranulin replacement therapy for frontotemporal dementia (FTD) patients with GRN mutations, addressing the critical knowledge gap between progranulin deficiency and TDP-43 pathology. The study employs a novel adeno-associated virus (AAV9) vector system designed to deliver functional progranulin across the blood-brain barrier, target

METHODOLOGY NOTES

Phase 1: Participant recruitment and screening (months 1-6) of 60 presymptomatic GRN mutation carriers and 40 early symptomatic patients through established FTD research networks. Inclusion criteria: pathogenic GRN mutations, age 25-65, CDR≤0.5. Phase 2: Baseline assessments (months 7-9) including comprehensive neuropsychological battery, MRI with DTI sequences, lumbar puncture for CSF biomarkers (progranulin, TDP-43 species, neurofilament light), and TDP-43 PET imaging using [18F]PI-2620 tracer. Phase 3: Randomization and treatment (months 10-12) with intrathecal administration of AAV9-GRN vector (low dose: 1×10^12 vg, high dose: 3×10^12 vg) or placebo via lumbar puncture under fluoroscopic guidance. Phase 4: Follow-up assessments at months 1, 3, 6, 12, 18, and 24 post-treatment including monthly CSF progranulin monitoring for first 6 months, then quarterly. Safety monitoring includes complete blood counts, liver function tests, and AAV capsid antibody titers. Phase 5: Biomarker analy

▸Metadatasource: {'type': 'manual', 'source_name': 'wiki'

source	{'type': 'manual', 'source_name': 'wiki', 'extracted_by': 'backfill_v1', 'extraction_date': '2026-04-16T01:00:16.900984Z'}
summary	# Progranulin Replacement Therapy for FTD — Vector Development and Validation ## Background and Rationale This clinical trial focuses on developing and validating progranulin replacement therapy for f
entities	{'genes': ['FTD'], 'diseases': ['ALS']}
model_system	human
_schema_version	1
experiment_type	clinical
primary_outcome	Dose-dependent increase in CSF progranulin levels from baseline to 6 months post-treatment, with target restoration to >50% of normal levels in GRN mutation carriers receiving AAV9-progranulin gene th
methodology_notes	Phase 1: Participant recruitment and screening (months 1-6) of 60 presymptomatic GRN mutation carriers and 40 early symptomatic patients through established FTD research networks. Inclusion criteria:
replication_status	conflicting
extraction_metadata	{'backfill_at': '2026-04-16T01:00:16.900989', 'needs_review': True, 'extraction_notes': 'Backfilled from wiki source (no PMID available)', 'extraction_confidence': 0.4}

📊 Evidence Profile Foundational

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100%

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623

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Progranulin Replacement Therapy for FTD — Vector Development and Validation

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