The PR006 program was founded on a strong genetic rationale: monoallelic null mutations, or, in rare instances, biallelic hypomorphic mutations in the GRN gene, result in haploinsufficiency with an approximately 50% reduction in progranulin levels and a virtually 100% risk of developing FTD typically beginning in the fifth or sixth decade of life3–6. This evidence concerns the gene GRN and frontotemporal dementia.