The Advancing Research And Treatment In Frontotemporal Lobar Degeneration (Artfl) North American Rare Disease Clinical Research Consortium: Progress And Characterization Of Initial Participants

Objective: To build a network of clinical research sites for frontotemporal lobar degeneration (FTLD) spectrum disorders and prepare for clinical trials of new therapeutic agents. Background: The ARTFL consortium aims to A) characterize the North American population of sporadic FTLD patients in preparation for clinical trials (Project 1) and B) characterize longitudinal changes in both asymptomatic and symptomatic familial FTLD (fFTLD) over one year to better understand these disorders and to develop new clinical trial outcome measures (Project 2). ARTFL works closely with the new FTD Disorders Registry (www.ftdregistry.org) for participant recruitment and characterization. Design/Methods: Participants are evaluated with a standardized battery including neurological exams and neuropsychological testing. DNA, plasma, mRNA, and PBMCs are collected and stored at the National Cell Repository for Alzheimer’s Disease. All participants are genotyped for FTLD-associated mutations. Asymptomatic family members undergo MRI. Familial participants return for in one year for follow-up. Results: 812 (401 female (49.4%)) participants have been evaluated at 16 sites through September 2017. Project 1 has enrolled 409 individuals with sporadic FTLD syndromes (mean age 65.9 years [range 34–89]), with the most prevalent phenotypes being bvFTD (32%) PSP (22%), and svPPA (14%), followed by nfvPPA (11%) and CBS (10%). The three largest groups were comparable on the Clinician’s Global Impression (CGI)-Severity rating but differed on Schwab and England ADL (svPPA>bvFTD>PSP) and PSP rating scale (PSP>>bvFTD>svPPA), with additional pairwise differences on Clinical Dementia Rating-Comportment (bvFTD>svPPA, PSP) and the traditional CDR-SB (bvFTD>svPPA). Project 2 has enrolled 286 asymptomatic (CDR=0; mean age 48.2) and 117 symptomatic (CDR>=0.5; mean age 58.8 years; mean CDR-SB: 5.03) participants with fFTLD. 169 (113 asymptomatic) have returned for longitudinal evaluation. Conclusions: ARTFL has characterized a substantial population of FTLD patients to support clinical and translational research. Clinical, biomarker, genetic, and imaging data are available to investigators worldwide, and increasingly, the network will support clinical trials. Study Supported by: The Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) Study receives support through a U.S Department of Health and Human Services (DHHS) and the National Institute of Neurological Disorders and Stroke (NINDS)/National Center for Advancing Translational Sciences (NCATS) grant U54NS092089. ARTFL works closely and shares an infrastructure with the Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) project, funded by the National Institute on Aging (NIA) grant U01AG045390 Disclosure: Dr. Boxer has nothing to disclose. Dr. Rosen has nothing to disclose. Dr. Boeve has received research support from GE Heathcare and Axovant. Dr. Heuer has nothing to disclose. Dr. Grossman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with GE Whitney. Dr. Grossman has received personal compensation in an editorial capacity for Neurology. Dr. Coppola has nothing to disclose. Dr. Dickerson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck, Lilly, Biogen, Piramal. Dr. Appleby has nothing to disclose. Dr. Bordelon has nothing to disclose. Dr. Brushaber has nothing to disclose. Dr. Dheel has nothing to disclose. Dr. Domoto-Reilly has nothing to disclose. Dr. Faber has nothing to disclose. Dr. Feldman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Medscape. Dr. Feldman has received research support from consulting service agreements with UCSD for Tau Rx, Merck, Eisai, Genentech, and Probiodrug (unpaid). Funding to the ADCS for clinical trials with Lilly, Toyama, and Biohaven. Dr. Fields has nothing to disclose. Dr. Fong has nothing to disclose. Dr. Foroud has nothing to disclose. Dr. Ghoshal has nothing to disclose. Dr. Graff-Radford has nothing to disclose. Dr. Hsiung has nothing to disclose. Dr. Huey has nothing to disclose. Dr Irwin has nothing to disclose. Dr. Kantarci has nothing to disclose. Dr. Kaufer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Axovant, Takeda, Abbvie. Dr. Kerwin has nothing to disclose. Dr. Klein has nothing to disclose. Dr. Knopman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck Pharmaceuticals and the DIAN study. Dr. Kornak has nothing to disclose. Dr. Litvan has received personal compensation for serving onthe scientific steering committee of the Biotie/Parkinson Study Group clinical trial Dr. Lungu has nothing to disclose. Dr. Mackenzie has nothing to disclose. Dr Mendez has nothing to disclose. Dr. Miller has nothing to disclose. Dr. Onyike has nothing to disclose. Dr. Pantelyat has nothing to disclose. Dr. Potter has nothing to disclose. Dr. Rademakers has nothing to disclose. Dr. Ramos has nothing to disclose. Dr. Rascovsky has nothing to disclose. Dr. Roberson has nothing to disclose. Dr. Sutherland has nothing to disclose. Dr. Tartaglia has nothing to disclose. Dr. Tatton has nothing to disclose. Dr. Toga has nothing to disclose. Dr. Weintraub has nothing to disclose. Dr. Wszolek has received personal compensation in an editorial capacity for Elsevier - Parkinsonism & Related Disorders, and Wiley - European Journal of Neurology. Dr. Wszolek has received royalty, license fees, or contractual rights payments from Mayo Clinic and I have a financial interest in technologies entitled, “Identification of Mutations in PARK8, a Locus for Familial Parkinson’s Disease” and “Identification of a Novel LRRK2 Mutation, 6055G>A (G2019S), Linked to Autosomal Dominant Par.