ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration, Cycle 2 (ALLFTD2)

Mayo Clinic Rochester, Rochester MN

Investigators

Linked publications & trials

Abstract

ABSTRACT – ALLFTD2: OVERALL SECTION Frontotemporal lobar degeneration (FTLD) is an overarching term for a group of neurodegenerative disorders associated with the accumulation of toxic protein aggregates in the CNS, most commonly comprised of one of two major proteins—microtubule associated protein tau (i.e., FTLD-tau) and TAR DNA binding protein molecular weight 43 (i.e., FTLD-TDP). FTLD is approximately as common as Alzheimer’s disease in those who manifest symptoms prior to age 65. FTLD is uniformly fatal, and there are no effective therapies that can slow or halt disease progression. Approximately 30% of all FTLD patients have a dominantly inherited familial disorder (f- FTLD), with the three most commonly mutated genes being microtubule associated protein tau (MAPT), progranulin (GRN), and chromosome 9 open reading frame 72 (C9orf72). Most new therapies will target one of these gene products. While there are no current clinical or biomarker findings that confidently predict the underlying proteinopathy in those with s-FTLD, it is likely that some of these agents might also be useful in sporadic (s-) FTLD, particularly if FTLD-tau and/or FTLD-TDP specific biomarkers are developed. Over the prior two grant cycles, the Advancing Research and Treatment in Frontotemporal Lobar Degeneration (ARTFL; U54 NS092089) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS; U01 AG045390) projects (abbreviated ARTFL/LEFFTDS; 2014-2019), and the current ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD; U19 AG063911, 2019-2025) have been successful in many regards, but numerous knowledge gaps remain. The current proposal represents our plan to continue and expand efforts in the renewal grant application: ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration, Cycle 2 (ALLFTD2). This program will expand the infrastructure and data collection methods by enrolling 1450 unique persons over 5 years (610 from f-FTLD kindreds and 840 with s-FTLD). Due to the lack of deep and frequent phenotypic data on key FTLD participants that is crucial for optimizing clinical trial design, a subset of participants in the late presymptomatic phase of f-FTLD, and early symptomatic phase of f- and s- FTLD, will undergo clinical, biofluid and imaging data/sample/scan collection every 3-6 months over a 12-month time span. The Cores will contribute data and expertise to the Projects, which will focus on asymptomatic/minimally symptomatic f-FTLD (Project 1) and mildly symptomatic s-FTLD (Project 2). If funded, the ALLFTD2 program will provide data/samples/scans/tissue to the greater scientific community while addressing several knowledge gaps relating to FTLD, with the ultimate goal of fostering development of effective treatments for those with FTLD.