Press Release

FOR IMMEDIATE RELEASE

Bluefield Launches Biomarker Study for Rare Disease Frontotemporal Dementia

SAN FRANCISCO, Aug 24, 2020 – Bluefield Project to Cure Frontotemporal Dementia today announces launch of The Neurofilament Surveillance Project (NSP). The NSP is a new, four-year clinical study that will gather information crucial for the development of therapies for frontotemporal dementia (FTD), also known as frontotemporal lobar degeneration (FTLD). FTLD is a rare but fatal adult-onset neurodegenerative disease that causes severe changes in an afflicted individual’s personality and ability to interact with others. Symptoms typically begin in middle-age and death usually occurs within 10 years after symptom onset. The NSP will measure the protein neurofilament light chain (NfL) in the blood of 335 study participants four times a year for three years. NfL is a protein found inside neurons and normally not present in the blood of healthy individuals. As FTLD symptoms begin, NfL levels in the blood increase. Participants in the NSP study must be members of a family with a disease-causing mutation in C9orf72, GRN or MAPT, but need not carry a mutation or know their mutation status.

Is there a cure for FTLD?

Although researchers are racing to develop therapies, there is currently no approved treatment or cure. Approximately 25% of FTLD is caused by a mutation in one of three genes: C9orf72, GRN or MAPT. Most therapeutic development is currently focused on these three genetic forms of FTLD because they provide a molecular entry route to understanding the disease. Individuals with genetic FTLD carry a disease-causing mutation from birth, but symptoms typically begin in middle-age. Identifying disease onset in time to respond is critically important to testing potential life-saving therapies. By the time FTLD has progressed enough to be clinically diagnosed, there has been a measurable loss in brain mass. Once lost, brain mass can never be replaced.

How will the Neurofilament Surveillance Project help advance a cure for FTLD?

With the Neurofilament Surveillance Project study, Bluefield aims to bridge clinical science and therapeutic development. By evaluating the blood of genetic FTLD participants, the NSP will help pinpoint the most effective time to initiate therapy. Certified research nurses will visit participants at their location of choosing to collect blood every three months for three years. In addition to NfL, other proteins may also be measured for potential biomarkers of FTLD onset and progression.

The NSP is an ancillary study of the larger ARTFL-LEFFTDS Longitudinal FTLD (ALLFTD) natural history study. ALLFTD is a comprehensive, NIH-funded study to characterize the natural history of FTLD in preparation for treatment trials. ALLFTD collects annual cognitive, imaging and behavioral assessment data, as well as blood and cerebrospinal fluid specimens. These ALLFTD data will be matched with NfL measurements collected by the NSP in order to better define the changes that occur with FTLD onset and progression. The NSP will directly inform efforts to find a cure.

“This important longitudinal study is a critical adjunct to the ALLFTD natural history study. The NSP will help us understand how NfL levels change in individuals with FTLD-causing mutations as they convert from presymptomatic to symptomatic neurodegenerative disease,” noted Dr. Adam Boxer, Endowed Professor of the Memory and Aging Center at University of California, San Francisco, and a lead investigator for the ALLFTD study. “The insight we will gain into NfL’s value as an indicator of disease state will help support the development of vital therapies.”

About Frontotemporal Lobar Degeneration

FTLD is the most common cause of early-onset neurodegeneration. While FTLD is generally considered rare and underdiagnosed, affecting just 5 to 22 of every 100,000 Americans, it comprises 10 to 20% of all suspected dementia cases. FTLD has a genetic component; approximately 25-40% of FTLD cases are inherited and occur within families. Inherited disease is typically caused by a mutation in one of three genes: Chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN), or tau (MAPT). The rest of FTLD cases occur sporadically, without a known disease-causing mutation.

Symptoms of FTLD usually first appear in late middle age, but can go unrecognized by friends and family. Because those who are afflicted are often considered “too young” for neurodegeneration and don’t experience memory loss like with other neurodegenerative diseases, early FTLD is commonly misdiagnosed. By the time FTLD is typically diagnosed, severe brain loss impacting an individual’s ability to function and communicate has already occurred.

FTLD comprises three clinical syndromes: behavioral variant frontotemporal dementia (bvFTD), semantic variant primary progressive aphasia (svPPA) and nonfluent variant primary progressive aphasia (nvPPA). bvFTD impacts information processing and behavioral regulation, leading to confusing changes in personality and unexpected decision-making and actions. Family members may notice apathy, a lack of empathy, or socially inappropriate behavior in their loved one. svPPA hinders an individual’s ability to recognize and name ordinary objects. nvPPA disrupts an individual’s ability to produce speech, and patients may stop speaking altogether. Some patients with nvPPA may also experience muscle weakness.

About the Study Funders

The NSP is funded and supported by a consortium of nonprofit foundations, small and large biotechs, and pharmaceutical companies exploring therapies for neurodegenerative diseases, in collaboration with academic researchers in the ALLFTD consortium. Study funders include: Alector, Arkuda Therapeutics, Biogen, the Bluefield Project to Cure Frontotemporal Dementia, Ionis Pharmaceuticals, Janssen Pharmaceuticals, Inc., Passage Bio and UCB Biopharma SRL.

Funding is also provided by the Alzheimer’s Drug Discovery Foundation (ADDF) Diagnostics Accelerator in collaboration with The Association for Frontotemporal Degeneration (AFTD). The ADDF's Diagnostics Accelerator is a research initiative supported by leading philanthropic partners and organizations to accelerate the development of affordable and accessible biomarkers to diagnose Alzheimer's disease and related dementias, and to advance the development of more targeted treatments. To learn more about the initiative visit the website at: AlzDiscovery.org/accelerator.

Additional consortium members may join as the study proceeds.

About the Bluefield Project to Cure FTD

The Bluefield Project to Cure Frontotemporal Dementia is a 501c3 nonprofit founded in 2010 to find a treatment or cure for FTLD caused by mutations in the progranulin (GRN) gene. It funds discovery, translational and clinical research and partners with industry to accelerate the development of therapies. Bluefield-funded research has resulted in over 130 peer-reviewed publications and catalyzed significant commercial interest in FTLD. The Bluefield Project also co-founded and provides ongoing support to the FTD Disorders Registry.

For further information, please contact:

Press
Laura Mitic, Chief Scientific Officer
laura.mitic@bluefieldproject.org

Study Participation
Rachel Acuna-Narvaez, Project Manager, Biomarker Development
rachel.acuna-narvaez@bluefieldproject.org