For Researchers

Today’s research can lead to tomorrow’s breakthroughs. In this section, you’ll learn about research funding opportunities, new AFTD initiatives, and more.

2016 Grants Funded Yearbook

The year 2016 was a crucial one for AFTD’s research funding programs.  It was the announcement of the first recipients of awards supported by the FTD Biomarkers Initiative. Through the support of these innovative research projects, AFTD seeks to advance the discovery and development of biomarkers that differentiate FTD from other neurodegenerative disorders, discriminate between FTD subtypes, identify underlying molecular pathologies, confirm pharmacodynamic modulation of disease pathways and track disease progression.

We also built on our long-standing partnership with the Alzheimer’s Drug Discovery Foundation (ADDF) to launch the Treat FTD Fund, a unique new funding opportunity focused on advancing the development of symptomatic and disease-modifying therapeutics through the support of clinical trials of novel or repurposed drugs. We look forward to announcing the first recipients of awards through the Treat FTD Fund in mid-2017. In light of this new funding initiative, our Accelerating Drug Discovery for FTD program was redirected to focus on preclinical research, including target validation, in vitro testing of promising novel and repurposed compounds, and the development of new animal and cellular models. This shift in focus aligns preclinical and clinical funding efforts in support of the common goal of accelerating FTD drug development.

2016 FTD Biomarkers Initiative Grant Recipients

Randall Bateman

“Human CNS tau kinetics in tauopathies”
Randall Bateman, MD
Washington University in St. Louis
Funding period: 2 years
Amount: $495,453
Project description: 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

“sTREM2, PGRN and GRN as CSF markers for microglial activity, disease progression and therapeutic target engagement”
Christian Haass, PhD
Ludwig-Maximilians University and DZNE
Funding period: 3 years
Amount: $450,000
Project description: 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

“Assessing poly(GP) proteins as clinical and pharmacodynamic biomarkers of C9orf72-associated FTD”
Leonard Petrucelli, PhD
Mayo Clinic – Jacksonville
Funding period: <2 years>
Amount: $300,000
Project description: 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

“Identification of novel biofluid markers of tau and TDP-43 pathology”
Jonathan Rohrer, MRCP, PhD
University College London
Funding period: 2 years
Amount: $238,686
Project description: 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

“Quantitative profiling of tau in CSF to pilot diagnoses and monitoring treatment effectiveness in FTD patients”
Judith Steen, PhD
Boston Children’s Hospital
Funding period: November 15, 2016 – November 14, 2018
Amount: $325,545
Project description: 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.

Judith Steen

“Using TDP43 as a biomarker in FTD patients”
Judith Steen, PhD
Boston Children’s Hospital
Funding period: November 15, 2016 – November 16, 2018
Amount: $189,455
Project description: 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.

2016 Pilot Grant Recipients

Basic Science Pilot Grant


“Tau and adult neurogenesis. Therapeutic potential for frontotemporal degeneration”
María Llorens-Martín, PhD
Center for Networked Biomedical Research in Neurodegenerative Diseases
Funding period: January 1, 2017 – December 31, 2017
Amount: $60,000
Project description:  In her Pilot Grant project, Dr. Llorens-Martín will use mice carrying an FTDP-17 tau mutation and viruses engineered to contain red, blue, or green fluorescent tracers to track the effect of this mutation on the development of new neurons in the hippocampus, one of the few brain regions that continues to generate brain cells throughout life. In addition, she will evaluate the potential of two kinds of interventions – environmental enrichment and artificial stimulation of brain cell maturation – for reversing mutation-related developmental changes.

Susan Marcus Memorial Fund Pilot Grant for Clinical Research


“Detection of misfolded TDP-43 protein in CSF and plasma of GRN and C9ORF72 mutation carriers”
Paola Caroppo, MD, PhD
RCCS Foundation Carlo Besta Neurological Institute
Funding period: January 1, 2017 – December 31, 2017
Amount: $60,000
Project description: Dr. Caroppo’s Pilot Grant project will develop a novel assay for the protein TDP-43, which forms abnormal aggregates in people with FTD-related mutations in the GRN or C9orf72 genes, using a technique originally developed to detect very small amounts of pathological proteins in prion diseases. She will then use this assay to study TDP-43 aggregation in individuals with FTD due to GRN or C9orf72 mutations and will also evaluate its value for detecting pathological TDP-43 in presymptomatic mutation carriers.

2016 AFTD-ADDF Accelerating Drug Discovery for FTD Grant Recipients

“Mitochondrial TDP-43 as a Novel Therapeutic Target for FTD”

Xinglong Wang, PhD
Case Western Reserve University
Funding period: March 1, 2017 – February 28, 2018
Amount: $150,000
Project description: The cytoplasmic mislocalization of TDP-43 represents a distinct key pathological feature of degenerating neurons in 50-70% patients with frontotemporal dementia (FTD). Our most recent study has revealed that TDP-43 accumulates in mitochondria in FTD patients and experimental models. And, importantly, the suppression of TDP-43 mitochondrial localization is sufficient to abolish the TDP-43 toxicity on mitochondria and neurons. In this study, we will use reprogrammed human neurons derived from patients bearing FTD-associated TDP-43 mutations, TDP-43 transgenic mice, a novel synthesized peptide inhibiting TDP-43 mitochondrial localization and a newly identified FDA-approved drug with significant inhibitory effects on mitochondrial TDP-43 in human neurons to test whether the suppression of TDP-43 mitochondrial accumulation could be a promising novel therapeutic approach for FTD patients. As the drug(s) to be identified has a history of safe use in clinical trials, repurposing of them may lead to novel therapeutic approaches for FTD.

“A novel neuroprotective compound targeting endogenous function of C9ORF72 in vivo”

Justin Ichida, PhD
University of Southern California
Funding period: <12 months>
Amount: $150,000
Project description: Frontotemporal Dementia (FTD) is the most frequently occurring dementia after Alzheimer’s Disease (AD), with an expected increasing prevalence due to the aging population. A GGGGCC repeat expansion in C9ORF72 is the most common genetic cause of FTD as well as a myotrophic lateral sclerosis (ALS), accounting for about 10% of each disease worldwide. Unfortunately, there are no effective therapeutic strategies available for either FTD or ALS. This proposal is focused on the development of a novel therapeutic strategy for FTD by testing a novel lead compound in relevant animal models as a preclinical proof-of-concept. Our lead compound was identified as highly neuroprotective in a high throughput small molecule screening using patient-derived induced neurons in our laboratory.