Biomarkers Consortium – Neurofilament as a Blood-Based Biomarker of Neurodegeneration in Familial Frontotemporal Degeneration (FTD)
Detecting the earliest stages of rare genetic neurodegenerative disorders
Frontotemporal degeneration (FTD) impacts the frontal and temporal lobes of the brain and is the most common form of dementia for people under 60. As their brain structure and function deteriorate, individuals may start losing control of their own behavior, experience limitations in speaking and understanding, or find it difficult to perform movement in their day-to-day activities. In addition to the multiple ways that symptoms can occur, the rate of symptom progression can vary significantly. Unfortunately for some, FTD begins in their 30s, dramatically disrupting their life trajectory. At present, there is no treatment or cure for FTD.
While the main cause of FTD is unknown, many people with the disease accumulate abnormal proteins which clump together in brain cells called neurons. When a neuron is damaged or dies, neurofilament (a normal protein component of the neuron) is released and the level of neurofilament increases in both cerebrospinal fluid and blood. Recent studies indicate that this increased neurofilament in the blood is a promising marker of the earliest stages of neurodegeneration. The ability to measure these forms of neurofilament will help identify when someone is at risk of developing symptoms, especially in people with genetic markers for rare neurodegenerative diseases such as familial FTD and amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease, a biologically related disease to FTD which this project will also examine).
Novel technological advances now present an opportunity to measure two forms of neurofilament: neurofilament light and phosphorylated neurofilament heavy. This project will evaluate whether these affordable and scalable blood tests are robust enough to confirm that blood levels of neurofilament light and phosphorylated neurofilament heavy can be used to determine the likelihood of FTD. Additionally, this project will advance new quality control materials to enable the standardization of measurements and interpretations across the blood tests over many years. Ultimately this will support clinical decision-making and accelerate the vitally needed development of therapeutics for patients with FTD and other rare neurodegenerative diseases.
- Food and Drug Administration
- National Institute on Aging
- National Institute of Mental Health
- National Institute of Neurological Disorders and Stroke
- Mayo Clinic
- Paris Brain Institute (ICM)/ AP-HP Pitié-Salpêtrière Hospital
- The Robert Packard Center for ALS Research at Johns Hopkins*
- University of California at San Francisco
- University of Gothenburg
- VU University Medical Center
- Alector, Inc*
- Biogen MA Inc.*
- Diagnostics Accelerator at the Alzheimer’s Drug Discovery Foundation*
- Otsuka Pharmaceutical Development & Commercialization, Inc.*
- Rainwater Charitable Foundation*
- The ALS Association*
- The Association for Frontotemporal Degeneration*
- The Bluefield Project to Cure Frontotemporal Dementia*
*Provides financial or in-kind support for this program.
- Evaluate next generation neurofilament assays to determine whether blood measures of neurofilament (neurofilament light and phosphorylated neurofilament heavy) are reliable in detecting the earliest rise in neurofilament.
- Advance the regulatory qualification of neurofilament light and phosphorylated neurofilament heavy as biomarkers to identify people at risk of FTD due to genetic and family connections and enable their participation in clinical trials of new therapies.