In 2017, AFTD was proud to announce the recipient of the first award through the new Treat FTD Fund, devoted exclusively to the support of FTD clinical trials. The year also marked another expansion of our Pilot Grant program, with the addition of a third Pilot Grant focused on novel non-pharmacological treatments and state-of-the-art diagnostic and monitoring technologies. A Request for Proposals for this new Pilot Grant was issued in January 2018 and the first awards will be made in Summer 2018. And in 2017, we were again fortunate to be able to make a positive contribution to the future of FTD research by funding two outstanding postdoctoral researchers.
2017 Treat FTD Fund Grant Recipients
“Non-invasive brain stimulation to restore cortical plasticity and connectivity in genetic and sporadic FTD”
Barbara Borroni, MD
University of Brescia
Project description: Dr. Borroni will test a treatment for FTD that is not a drug, but rather a noninvasive, painless form of brain stimulation known as transcranial direct current stimulation (tDCS), which uses electrodes placed on the scalp to deliver a low-intensity current that modifies brain activity. She hypothesizes that tDCS will have beneficial effects on FTD symptoms and delay disease onset in presymptomatic gene carriers.
2017 Pilot Grant Recipients
Basic Science Pilot Grant
“Accelerating tau pathogenesis in a new mouse model of frontotemporal dementia”
Todd Cohen, PhD
University of North Carolina at Chapel Hill
Funding period: January 1, 2018 – December 31, 2018
Project description: Dr. Cohen will use mice that have been genetically engineered to produce mutant tau proteins studded with add-ons known as acetyl groups — an abnormality that makes them highly toxic and mimics one of the features of the harmful tau proteins found in FTD. He anticipates targeting the proteins that control these aberrant modifications can help to identify new therapies that reduce tau pathology and prevent cognitive impairments in people with FTD.
Susan Marcus Memorial Fund Pilot Grant for Clinical Research
“Ambulatory assessment of sleep disorders in FTD”
Haakon Nygaard, MD, PhD
University of British Columbia
Funding period: January 1, 2018 – December 31, 2018
Brief description of project: Dr. Nygaard will examine sleep abnormalities — a common, but poorly understood clinical feature of FTD — using two portable recording devices: an actigraphy watch and a specially designed electroencephalogram (EEG) headband. This approach will allow him to monitor changes in the sleep patterns and circadian rhythm of participants in their own homes — changes that could ultimately aid diagnosis or lead to a biomarker to assess the effectiveness of new treatments.
2017 – 2019 AFTD Postdoctoral Fellowship Recipients
“Identification and validation of novel MAPT splicing factors and RNA-binding proteins”
Kathryn Bowles, PhD
Icahn School of Medicine at Mt. Sinai
Sponsoring PI: Alison Goate, D.Phil
Funding period: July 1, 2017 – June 30, 2019
Project description: Six varieties, or isoforms, of the protein tau, which forms abnormal accumulations in the nerve cells of about 40% of people with FTD, are found in the human brain. The isoforms result from slight differences in segments of the tau gene MAPT that are skipped during its formation. This “splicing” process, the factors that regulate it, and the role of disrupted splicing in FTD are not well understood. In her postdoctoral research project, Dr. Bowles will probe the human genome to identify genes for RNA-binding proteins and proteins known as splicing factors that control MAPT splicing. These proteins could represent novel targets for the development of drugs that “rebalance” the ratio of tau isoforms in FTD.
“Nucleocytoplasmic transport defects perturb granular flux in FTD”
Joseph-Patrick Clarke, PhD
University of Pittsburgh
Sponsoring PI: Christopher Donnelly, PhD
Funding Period: July 1, 2017 – June 30, 2019
Project description: In addition to forming abnormal aggregates in FTD, the proteins TDP-43 and Fused in Sarcoma (FUS), which are normally found in the cell nucleus, are mistakenly redirected to the cytoplasm, where they contribute to the formation of particles known as stress granules that may be “ground zero” for the initiation of TDP-43 or FUS accumulation. Dr. Clarke will utilize neurons generated from patient-derived induced pluripotent stem cells (iPSCs) with mutations in the C9ORF72, GRN, or MAPT genes to look for defects in the mechanisms that regulate the transport of proteins between the nucleus and cytoplasm and to determine whether such defects lead to stress granule formation. He will then test drugs known to alter nucleus-to-cytoplasm transport to learn if they can correct genetic defects in transport, block abnormal protein accumulation, and promote the survival of affected neurons. This research will improve our understanding of the cellular mechanisms affected in FTD and could lead to novel treatments.
2017 AFTD-ADDF Accelerating Drug Discovery for FTD Grants
“Novel human FTLD neuron and microglia cell models for drug discovery”
Steven Finkbeiner, MD, PhD
J. David Gladstone Institutes
Project description: Dr. Finkbeiner will monitor neurons and the brain’s immune cells, known as microglia, generated in the laboratory from patient-derived stem cells with a mutation in the progranulin gene, using a robotic microscopy technique that allows him to follow changes in individual cells over time. Specifically, he’ll be tracking fluctuations in the accumulation of FTD-associated proteins, inflammation, cell function, and cell survival. His goal is to develop laboratory models of FTD that accurately replicate the cellular features of the disease as the basis for a high-throughput assay to screen new drugs.