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.

Grants Funded

2019 Award Recipients

Pilot Grants

Nonpharmacological Therapies and Tools

“Improving the ability of family caregivers to care for persons living with frontotemporal dementia through an innovative simulation program”
Linda Wilson, PhD
Drexel University
Funding period: July 1, 2019 – June 30, 2020
Amount: $60,000
Project Description: Coping with FTD symptoms can be difficult and distressing for caregivers, who often know little about the disease or effective ways to address challenging behaviors. Dr. Wilson’s project will seek to give family caregivers the knowledge and skills needed to deal confidently with FTD symptoms through the use of simulated care scenarios that replicate challenging situations they encounter in daily life. Dr. Wilson will follow up with participants to determine how well the skills learned in the simulation laboratory transfer to the home setting and hopes to ultimately develop a standardized simulation program that can be used by community-based organizations serving families with FTD.

Basic Science

“Investigating the role of lysosomal progranulin in FTD”
Andrew Arrant, PhD
University of Alabama at Birmingham
Funding period: January 1, 2020 – December 31, 2020
Amount: $60,000
Project Description: Mutations in the progranulin (GRN) gene, one of the most common causes of genetic FTD, lead to a reduction in the progranulin protein it encodes and a corresponding loss of progranulin’s protective and anti-inflammatory actions. However, it is unclear whether the beneficial effect of progranulin is due to its interaction with progranulin receptors on the surface of cells or to its activity inside cells, where it regulates the function of lysosomes. Dr. Arrant will attempt to answer this question using a novel form of human progranulin that only acts on lysosomes to determine if this restricted form of the protein can rescue neurons derived from mice with a progranulin mutation. In addition, he will develop mice genetically engineered to express lysosome-specific progranulin to further study the interaction between lysosome function and neurodegeneration.

Susan Marcus Translational Research

“Optimization of bifunctional anti-tau intracellular antibody delivery into human neurons”
David Butler, PhD
Regenerative Research Foundation

Funding period: January 1, 2020 – December 31, 2020
Amount: $60,000
Project Description: The defining pathological feature of FTD-tau, one of a group of neurodegenerative disorders known collectively as tauopathies, is the abnormal accumulation of tau in neurons. The goal of Dr. Butler’s project is to develop genetically engineered intrabodies – antibodies designed to bind to targets inside cells rather than on the cell surface – that recognize tau and also contain a molecular tag that diverts the bound tau to the cell’s normal degradation pathway. As a result, toxic tau is broken down rather than accumulating. Dr. Butler will determine the safety and efficacy of these tau-lowering intrabodies in 3-dimensional human organoids, or “mini-brains,” derived from patient-specific induced pluripotent stem cells, the first step in developing intrabody-based therapeutics.

FTD Biomarkers Initiative

“Accelerating tau PET imaging through head to head comparison of novel radiotracers”
Tammaryn Lashley, MD, PhD and Kerstin Sander MD
University College London

Funding period: December 14, 2018 – December 13, 2020
Amount: $247,272

“Cryo-electron microscopy of brain-derived TDP-43 filaments to rationally design PET ligands for FTD”
Anthony Fitzpatrick, PhD
Columbia University Medical Center

Funding period: November 1, 2018 – October 31, 2019
Amount: $150,000

“Assessing poly(GP) proteins as clinical and pharmacodynamic biomarkers of C9ORF72-associated FTD”
Leonard Petrucelli, PhD
Mayo Clinic Jacksonville

Funding Period: October 1, 2019 – September 30, 2021
Amount: $565,248

“Targeting structural alterations of TDP-43 and other proteins to develop biomarkers for FTLD subtypes”
Magdalini Polymenidou, PhD
University of Zurich, Switzerland

Funding Period: September 1, 2019 – August 31, 2022
Amount: $532,122

AFTD Postdoctoral Fellowships (2019-2021)*

Basic Science

“A structural approach to rescuing C9orf72 haploinsufficiency in ALS/FTD”
Ming-Yuan Su, PhD
The Regents of the University of California

Funding period: July 1, 2019 – June 30, 2021
Amount: $110,000 USD ($55,000/year)
Project Description: The C9orf72 protein encoded by the C9ORF72 gene mutated in hereditary FTD and ALS exists as part of a large stable complex with two other proteins, SMCR8 and WDR41.  In her postdoctoral project, Dr. Su will utilize cryo-electron microscopy to determine the structure of this C9orf72SMCR8WDR41 complex and another technique, HDX-coupled mass spectrometry, to learn more about how the three proteins interact.  She will then attempt to identify small molecule compounds that can stabilize the complex, slowing its breakdown, and determine if stabilization can compensate for the reduction in C9orf72 due to the mutation in FTD and improve the survival of neurons created from patient-derived stem cells. If so, these compounds could be the starting point for the development of effective treatments for FTD associated with the C9orf72 mutation.

Clinical Research

“Identification of an RNA-based biomarker for FTD”
Oriol Dols Icardo, PhD
Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau

Funding period: January 1, 2020 – December 31, 2021
Amount: $110,000 USD ($55,000/year)
Project Description: The abnormal accumulation of tau, TDP-43, and other proteins that is the defining pathological feature of FTD may be preceded by alterations in RNA expression. Such changes in RNA could be a potential biomarker for early-stage FTD. In his postdoctoral project, Dr. Icardo will characterize the transcriptome of the frontal cortex in FTD-tau, FTD-TDP-43, and FTD-FUS compared to healthy controls. He will also compare TDP-43 associated RNA alterations in FTD with RNA alterations in the motor cortex of people with ALS. FTD-specific changes identified in brain will be further evaluated in RNA from exosomes of patients representing FTD clinical subtypes. Differences in CSF RNA that reliably and consistently differentiate FTD subtypes or individuals with FTD from those who do not could be the basis of a fluid biomarker as well as promising targets for RNA-based FTD treatments.

*First year independent fellowships awarded in basic and clinical research

2018 Award Recipients

Pilot Grants

Basic Science

“A C. elegans model to study the disease-producing effects of dipeptide repeats from the C9ORF72 locus”
Paschalis Kratsios, PhD
University of Chicago

Funding period: January 1, 2019 – December 31, 2019
Amount: $60,000
Project description: A mutation in the gene C9ORF72 is the most common cause of familial FTD and ALS. The mutation is an unusual one because it involves the repetition of a DNA sequence that results in the production of abnormal proteins known as dipeptide repeats (DPRs). Although DPRs are thought to play a key role in the disease process, it remains unclear how they trigger FTD and ALS pathology. In this project, Dr. Kratsios will try to better understand the factors that control the generation of DPRs, using a novel animal model: transgenic worms (Caenorhabditis elegans) carrying the C9ORF72 mutation. If successful, this research could identify new targets for drug development and support the use of C. elegans as a model organism in FTD research.

Susan Marcus Translational Research

“Identification of Target Genes Regulated by TDP-43 in Human FTD Brains”
Liam Chen, MD, PhD
Johns Hopkins University

Funding period: January 1, 2019 – December 31, 2019
Amount: $60,000
Project Description: During the processing of mRNA, segments needed for protein synthesis, known as exons, are spliced together following the removal of the intervening segments. One of the important roles of TDP-43 is to prevent the accidental inclusion of the deleted fragments. This protective function of TDP-43 is lost in FTD; as a consequence, these fragments, known as cryptic exons, remain in the final mRNA template – an error linked to neurodegeneration. Dr. Chen will seek to identify FTD-associated cryptic exons in post-mortem brain tissue from persons with FTD caused by mutation of the C9ORF72 gene. FTD-specific cryptic exons could potentially serve as biomarkers or as starting points for new treatments.

Nonpharmacological Therapies and Tools

“Development of a goal-directed behavior app: Changing apathy into action in frontotemporal degeneration”
Lauren Massimo, PhD, CRNP
University of Pennsylvania School of Nursing

Funding period: July 1, 2018 – June 30, 2019
Amount: $60,000
Project Description: Apathy, one of the most disabling symptoms in bvFTD, is estimated to occur in over 90% of people with this diagnosis and contributes significantly to caregiver burden. Dr. Massimo’s project will focus on the development of a novel intervention for apathy: a mobile app designed to increase motivation, promote self-care as well as other common daily activities, and support planning and carrying out these activities. The app will allow each patient-caregiver team to select personally meaningful goals for improvement, then engage and support the individual with FTD in working toward attaining these goals through the use of alerts prompting them to initiate activities, tools like calendars and checklists to assist them in planning, and a system of rewards to provide motivation. Dr. Massimo will conduct a 3-month pilot study of the app to evaluate its effectiveness in reducing apathy; improving activity levels, psychological functioning, cognition, and quality of life; and relieving caregiver burden.

FTD Biomarkers Initiative

“Individualized clinical and MRI endpoints for clinical trials in frontotemporal lobar degeneration, a pilot study”
Adam Boxer, MD, PhD and Howie Rosen, MD
University of California San Francisco

Funding period: June 1, 2018 – May 31, 2020
Amount: $249,965

Previous Grant Recipients