Frontotemporal Lobar Degeneration (FTLD) is a group of rare, fatal brain diseases that cause thinking and movement problems and for which there are currently no effective therapies. This project will build a North American clinical research network to prepare for studies of new FTLD treatments. Developing FTLD therapies may also help to find a cure for more common disorders such as Alzheimer's disease.
Frontotemporal Lobar Degeneration (FTLD) is the neuropathological term for a collection of rare neurodegenerative diseases that correspond to four main overlapping clinical syndromes: frontotemporal dementia (FTD), primary progressive aphasia (PPA), corticobasal degeneration syndrome (CBS) and progressive supranuclear palsy syndrome (PSPS). There are currently no effective FTLD therapies, although new drugs are reaching the stage where clinical trials are warranted. The overarching goal of this proposal is to build a FTLD clinical research consortium (FTLD CRC) to support the development of FTLD therapies. The FTLD CRC will be headquartered at UCSF and will partner with six patient advocacy groups to manage the consortium. Patients will be evaluated at 13 clinical sites throughout North America, and a genetics core will genotype all individuals for FTLD associated genes. Clinical research projects will focus on specific FTLD syndromes where there is a strong correlation between clinical syndrome and underlying pathology, who are targeted for enrollment in new trials. Research Project 1 will collect cross-sectional data in sporadic FTLD patients using a new FTLD assessment battery, as well as screening all individuals for known FTLD-causing mutations and evidence of systemic inflammation, to prepare for trials of anti-tau and anti-inflammatory agents. Research Project 2 will collect longitudinal clinical and MRl data on familial FTLD (f-FTLD) individuals who carry mutations in MAPT, GRN and C90RF72 and their asymptomatic family members to enable disease prevention clinical trials. Our specific aims are to: 1) build a FTLD clinical trials network to facilitate the design and conduct of clinical trials; 2) determine the clinical, genetic and systemic inflammatory cytokine profile of sporadic FTLD targeted for new trials: semantic variant PPA, FTD with amyotrophic lateral sclerosis and PSPS; 3) determine the natural history of asymptomatic and symptomatic f-FTLD patients using novel clinical measures and MR imaging over one year; 4) obtain pilot data using the new tau PET imaging agent PBB3 in FTLD, and other novel FTLD biomarkers and clinical tools that may be employed in future trials; 5) train clinical researchers focused on FTLD therapeutic development.