Biomarkers—characteristics that can be objectively measured for use as indicators of underlying biological or pathological processes—enable clinicians and researchers to accurately diagnose disease, monitor disease progression, and assess treatment outcomes. The current lack of biomarkers for FTD disorders results in diagnostic delays and errors, and frustrates drug discovery.
The FTD Biomarker Initiative, a major AFTD funding opportunity, supports innovative approaches to the discovery and development of urgently needed FTD biomarkers.
Proposals submitted to the FTD Biomarkers Initiative can target:
- Disorders across the FTD spectrum
- Any underlying disease mechanism
- Any approach with potential translational impact
- All stages of development, from preclinical to advanced
The FTD Biomarkers Initiative has invested in a long-term partnership with the Diagnostics Accelerator, a collaborative venture philanthropy program founded by the Alzheimer’s Drug Discovery Foundation (ADDF), to hasten the development of biomarkers for the early, effective diagnosis of FTD. A $2.5 million investment from AFTD will be matched dollar-for-dollar by Diagnostics Accelerator partners including Bill Gates, ADDF co-founder Leonard A. Lauder and other philanthropists. The result will be $5 million in additional funding dedicated specifically to developing biomarkers for FTD, within an initiative that will provide more than $35 million toward more effectively diagnosing all forms of dementia.
Timeline — 2016 Awards
To further discuss the application process or the financial or scientific aspects of proposals, please contact:
Debra Niehoff, PhD, Research Manager, AFTD
Phone: 267-758-8654 / Email: [email protected]
2016 FTD Biomarkers Initiative Award Recipients
Randall Bateman, MD: Washington University St. Louis
Human CNS tau kinetics in tauopathies (2 years, $495,453). Abnormal accumulation of the protein tau occurs in Alzheimer’s disease, FTD and other neurodegenerative disorders, leading to the characterization of these diseases as tauopathies. Disease-specific alterations in the ratio of various types (isoforms) of tau are thought to be a feature that differentiates the various tauopathies. An FTD-specific pattern of tau isoforms could be the basis for a biomarker to support the evaluation of tau-based therapeutics. Dr. Bateman’s project will examine the production and clearance of tau in PSP, CBD and at-risk individuals with FTD-associated gene mutations. To do this, he will use a technique known as Stable Isotope Labeling Kinetics (SILK).
Christian Haass, PhD: Ludwig-Maximilians University and DZNE
sTREM2, PGRN and GRN as CSF markers for microglial activity, disease progression and therapeutic target engagement (3 years, $450,000). Mutations in two genes – GRN (progranulin) and TREM2 (triggering receptor expressed on myeloid cells 2) encode proteins that are secreted by microglia, a type of immune cell in the brain. Because inflammation is thought to play a role in the development of FTD and other neurodegenerative disorders, inflammatory proteins are promising biomarker candidates. Dr. Haass’s project will take advantage of highly specific and sensitive antibody-based assays for progranulin (PGRN, the product of the GRN gene) and soluble TREM2 (sTREM2) along with novel antibodies specific for granulins (GRNs), the small peptides derived from progranulin.
Leonard Petrucelli, PhD: Mayo Clinic Jacksonville
Assessing poly(GP) proteins as clinical and pharmacodynamic biomarkers of C9orf72-associated FTD (2 years, $300,000). A mutation in the C9orf72 gene has been identified as the most common cause of familial FTD and ALS. In affected individuals, the mutated gene contains a short segment of nucleotides, GGGGCC, that is repeated hundreds of times. Abnormal transcription of this recurrent G4C2 segment leads to the production of abnormal proteins; poly(GP) proteins are one example. Poly(GP) proteins are thought to play a key role in the pathogenesis of FTD and are therefore an emerging target for drug development. Dr. Petrucelli will use a new state-of-the-art technology, single molecule array (Simoa), capable of detecting a single protein molecule to detect the poly(GP) proteins in blood and CSF.
Jonathan Rohrer, MD, PhD: University College London
Identification of novel biofluid markers of tau and TDP-43 pathology (2 years, $238,686). The ability to differentiate individuals with FTD-tau pathology from those with FTD-TDP-43 pathology is essential for the development of tau- or TDP-43-specific therapeutics. However, at the present time, it is only possible to accurately determine if a given person has FTD-tau or FTD-TDP-43 if they are known to have a genetic mutation in the MAPT gene (tau) or the GRN or C9ORF72 genes (TDP-43). Dr. Rohrer’s project will identify protein isoforms and protein fragments specific to tau and TDP-43 that can be used to develop ultrasensitive assays for use in CSF and blood.
Judith Steen, PhD: Boston Children’s Hospital
Quantitative profiling of tau in CSF to pilot diagnoses and monitoring treatment effectiveness in FTD patients (2 years, $325,545). Dr. Steen’s laboratory has developed a promising technique specifically for identifying and measuring abnormally modified forms of tau, called the FLEXITau assay, which has been shown to accurately distinguish FTD subtypes from Alzheimer’s disease and healthy controls in post-mortem brain tissue. In this project, Dr. Steen will fine-tune the FLEXITau assay and extend testing to CSF samples with the goal of characterizing disease-specific patterns that can be used to differentiate FTD from other neurological diseases.
Using TDP43 as a biomarker in FTD patients (2 years, $189,455). Dr. Steen’s second project will leverage the experience gained during the development of the FLEXITau assay to develop a similar FLEXI assay for TDP-43 modifications. The new FLEXITDP43 assay will be tested on brain tissue samples from FTD patients and samples from patients with other neurodegenerative disorders and optimized to establish a foundation for future evaluation in biofluids.