Sandler Neurosciences Center at UCSF

The ARTFL administrative unit is located at the University of California, San Francisco in the Sandler Neurosciences Center pictured here

About

The Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) consortium is an integrated group of academic medical centers partnered with patient support organizations and dedicated to conducting clinical research in sporadic and familial frontotemporal lobar degeneration (FTLD) syndromes. ARTFL is funded by the National Institutes of Health and is part of the Rare Diseases Clinical Research Network. The operations of the ARTFL consortium are based at the University of California, San Francisco, and there are currently fourteen clinical study sites in the United States and Canada.

The ARTFL project will establish a large cohort of patients with FTLD syndromes including Corticobasal Degeneration Syndrome (CBD or CBS), primary progressive aphasias (PPA) including semantic variant (svPPA) and non-fluent variant (nvPPA), behavioral variant Frontotemporal Dementia (bvFTD), Frontotemporal Dementia with Amyotrophic Lateral Sclerosis (FTD-ALS), and Progressive Supranuclear Palsy (PSP). Healthy family members of patients with genetic causes of FTLD will also be enrolled.

Approximately 1,560 patients and family members will participate in on-site evaluations that will include medical exams, clinical assessments of cognition and functioning, questionnaires and surveys, and biological specimens. Patients and family members with familial FTLD syndromes may be followed longitudinally. Using the cohort data, we will conduct projects to discover new biomarkers for disease activity, standardize diagnostic criteria, and identify a large group of potential participants for clinical trials of new targeted therapeutic agents. Patients do not need to be enrolled in all studies to participate in ARTFL activities.

All of the participating ARTFL centers are expert centers for the diagnosis and management of FTLD syndromes. The primary purpose of the ARTFL consortium is to conduct research, but it is anticipated that patients and their doctors may be interested in clinical evaluation as well as research participation.

The generous support of the NIH has provided us with the resources necessary to create this ongoing clinical research infrastructure and the ARTFL investigators are excited to be involved in this large collaborative effort.


Mission

The mission of the ARTFL project is to conduct clinical research to learn more about the different frontotemporal lobar degeneration (FTLD) spectrum diseases to support the development of new therapies and diagnostic tools. We also aim to assist patients and family members to manage these diseases by connecting them with patient advocacy groups, expert medical care, support services and new research opportunities, in particular clinical trials.


Goals

The goals of this consortium are to:

  • Characterize the available pool of FTLD patients with clinical syndromes that are amenable to clinical trials by enrolling them into an observational cohort study to collect clinical, biomarker and cognitive assessments
  • Identify the barriers to clinical trial participation for FTLD patients and caregivers
  • Establish a patient contact registry for patients, family members and caregivers
  • Develop improved clinical tools and biomarkers for studying FTLD
  • Discover new genes, risk factors and markers of disease and disease progression that will lead to better treatments and deeper scientific understanding of these syndromes
  • Work with patient advocacy groups to help patients and family members participate in research and improve care of FTLD patients
  • Provide anonymized specimens and clinical data to other scientists to promote new research in FTLD
  • Train new investigators in the field of FTLD research
  • Foster novel research approaches to FTLD by supporting Pilot Projects

LEFFTDS

ARTFL LEFFTDS


ARTFL is closely connected with another study aimed at understanding familial frontotemporal lobar degeneration (FTLD) called Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS). This study (AG045390) is a U01 project being jointly led by the Mayo Clinic Rochester and UCSF and jointly funded by the NIA and NINDS. LEFFTDS is enrolling 300 participants from families with known mutations in one of the three genes most commonly associated with FTLD: microtubule associated protein tau (MAPT, sometimes also referred to as “Tau”), GRN, and C9ORF72. The 300 LEFFTDS participants are a subset of the ARTFL enrollees. The clinical and imaging procedures for LEFFTDS and ARTFL are identical. The studies share the same clinical, imaging and biological specimens repositories. The biomarker protocols are identical as well but LEFFTDS collects more types of biological specimens than ARTFL. Compared with ARTFL, LEFFTDS is more focused and intense. While ARTFL is enrolling participants with a strong family history of FTLD regardless of whether a mutation has been found in that family, LEFFTDS is only enrolling families where a known mutation has been found in one of the three targeted genes. Both studies are enrolling symptomatic and asymptomatic family members. While LEFFTDS is seeing each patient for three annual visits and acquiring brain imaging at each visit, ARTFL is seeing family members twice over one year and is only acquiring imaging in asymptomatic patients. All participants in LEFFTDS will be asked to contribute CSF (have a lumbar puncture) while this is currently only occurring in ARTFL patients with symptomatic Progressive Supranuclear Palsy. LEFFTDS collects Peripheral Blood Mononuclear Cells (PBMCs) suitable for generation of induced pluripotent stem cells and RNA suitable for gene expression analysis, while ARTFL does not. The database containing the ARTFL data will also include an indication of whether this participant is a LEFFTDS coenrollee. The table below compares the two protocols.


    ARTFL LEFFTDS
Number   1560 300 (subset of ARTFL)
Populations Sporadic FTLD YES NO
GENETIC FTLD YES YES
ENROLLMENT CRITERIA FAMILY HISTORY KNOWN MUTATION IN FAMILY
Symptomatic Familial FTLD YES YES
Asymptomatic Familial FTLD YES YES
Genes Targeted ANY, KNOWN or UNKNOWN MAPT, GRN, C9ORF72
Design Time points Sporadic 1 No
Time Points Familial 2 3
Procedures Imaging Sporadic PSP Only NA
Imaging Symptomatic Familial No x3
Imaging Asymptomatic Familial x2 x3
DNA Sporadic Yes NA
DNA Familial Yes Yes
PBMCs Yes Yes
Plasma Sporadic Yes No
Plasma Familial Yes Yes
RNA Yes Yes
CSF PSP Yes
Serum Yes Yes