The Kissick Family Foundation Frontotemporal Dementia (FTD) Grant Program and the Milken Institute Science Philanthropy Accelerator for Research and Collaboration (SPARC) are pleased to announce that six research teams have been awarded grants to advance scientific understanding of FTD, totaling $3 million in new funding for this disease.

Research projects supported by the Kissick Family Foundation FTD Grant Program

Sami Barmada, MD, PhD, University of Michigan, Michigan, USA
Co-Investigator: Shyamal Mosalaganti, PhD, University of Michigan Life Sciences Institute, Michigan, USA

This project, Structural Insights into TDP-43 Aggregation and Lysosomal Dysfunction in FTD, will provide high-resolution insight into the structures of the irregular proteins (TDP-43) to better understand how these proteins malfunction in the brain to cause FTD. The results of this work could eventually inform imaging studies for detecting TDP-43 protein malformation, for example, to serve as a biomarker for FTD, and the development of therapies that directly act on TDP-43.

Martin Kampann, PhD, University of California San Francisco, California, USA

The grant to examine Systematic Elucidation of Mechanisms Underlying Genetic Risk for Sporadic FTD aims to better understand the genetic variants that create risk for the disease, especially those that have not been fully established. This project will examine the genetic pathways in different brain cell types to characterize their relevance to mechanisms of FTD and could uncover new factors associated with sporadic forms of FTD, where a genetic link is unknown.

Maura Malpetti, PhD, University of Cambridge, Cambridge, UK
Co-Investigator: James Rowe, MD, PhD, University of Cambridge, Cambridge, UK
Co-Investigator: John O’Brien, MD, DM, University of Cambridge, Cambridge, UK
Co-Investigator: Alexander Murley, MD, PhD, University of Cambridge, Cambridge, UK

This grant supports the ON-FIRE: Open Network for Frontotemporal Dementia Inflammation Research consortium led by Malpetti. This consortium consists of a large multi-site (22+ locations) study that will collect data from over 300 patients. This research team seeks to examine biomarkers in the blood to identify inflammation “fingerprints”, linking patterns of neuroinflammation with symptoms and progression in FTD. If successful, the FTD-specific neuroinflammation signatures will create a biomarker for predicting disease progression, designing clinical trials, and identifying targets for new treatments.

Leonard Petrucelli, MD, PhD, Mayo Clinic College of Medicine and Science, Florida, USA
Co-Investigator: Michael Ward, MD, PhD, National Institutes of Health, Maryland, USA

This study, Determining the Impact of TMEM106b fibrils on FTLD Pathogenesis, aims to better understand how certain genetic variants create vulnerabilities for the disease. It will elucidate how a genetic variant (TMEM106b-T185S) and its resulting protein (TMEM106b) confer an increased risk of FTD. The research team seeks to characterize how protein fibrils, formed when proteins misfold and aggregate, affect neurons and contribute to disease.

James Shorter, PhD, University of Pennsylvania Perelman School of Medicine, Pennsylvania, USA
Co-Investigator: Chris Donnelly, PhD, University of Pittsburgh School of Medicine, Pennsylvania, USA
Co-Investigator: Robert Kalb, MD, Northwestern University Feinberg School of Medicine, Illinois, USA

This project, Defining Oligonucleotide Therapeutics that Reverse TDP-43 Proteinopathy, looks to optimize a potential therapy—“short RNAs”—that could reverse malfunctioning in some proteins (TDP-43) implicated in FTD. The team will test the therapy in three models—at the protein level, in human neurons, and in mice—and determine its potential as a therapeutic candidate. These short RNAs could provide an alternative treatment option that addresses malfunctioning TDP-43 without damaging its essential function, thus overcoming limitations of currently FDA-approved therapeutics.