The Phenotype-Genotype-Biomarker (PGB, or PGB1) study (<a href="https://clinicaltrials.gov/study/NCT02327845">NCT02327845</a>) of the <a href="https://create.rarediseasesnetwork.org/">Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium</a> was a natural history and biomarker study of patients with amyotrophic lateral sclerosis (ALS) or a related disorder, including but not limited to ALS-frontotemporal dementia (ALS-FTD), progressive muscular atrophy (PMA), primary lateral sclerosis (PLS), hereditary spastic paraplegia (HSP), and multisystem proteinopathy (MSP). In addition to patients enrolled in the PGB1 Cohort (primary participants), the study also enrolled family members for limited data collection (secondary participants). A primary goal of the study was to pair detailed longitudinal phenotypic data (motor and cognitive/behavioral) with whole genome sequence data, to permit exploration of phenotype-genotype associations. A second primary goal was to combine the phenotypic (and, as needed, genomic) data with an array of longitudinally collected biological samples (e.g. serum, plasma, urine, cerebrospinal fluid), to permit development and validation of biomarkers with well-defined contexts-of-use to aid therapy development for ALS and related disorders. The PGB1 Cohort (primary participants) was enrolled between 2015 and 2019, at 13 centers in the United Sates, 1 in South Africa, and 1 in Germany. Phenotypic data included demographics; onset characteristics (e.g., age and site of symptom onset); disease severity at the time of enrollment; and functional decline (e.g., longitudinally measured revised ALS functional rating scale [ALSFRS-R] scores, slow vital capacity [SVC], Edinburgh Cognitive and Behavioral ALS Screen [EACAS] data, and Spastic Paraplegic Rating Scale [SPRS] as appropriate). Periodic medical record reviews, in addition to direct communication with patients and family, were performed as needed, to ascertain the timing of survival endpoint (permanent assisted ventilation [PAV; non-invasive ventilation >23 h/day], tracheostomy, or death). This submission to dbGaP includes data from N=705 in PGB1, including N=472 ALS/ALS-FTD, N=20 PMA, N=47 PLS, N=162 HSP, and N=4 with other related disorders.

Phenotype Genotype Biomarkers (PGB)

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