Neurofilaments – Unlocking advances in neuroscience

Leaders from the diverse worlds of science and politics have heralded the arrival of a “golden age” of neuroscience. Cutting-edge research is not only enhancing our understanding of the central nervous system, including the brain; it is also driving major advances in medical technology that hold the potential to change the way we diagnose, treat and care for people living with deadly neurological conditions.

One of the most promising developments has been the discovery of a biomarker prevalent among many devastating neurodegenerative diseases – neurofilament. Through the measurement and understanding of neurofilaments, scientists like myself are opening new doors to investigate these diseases, monitor their progression, and develop new therapies. Neurofilaments are proteins that form an essential building block of neurons, which link together to create communications pathways that transmit signals across the brain and spinal cord.¹ This complex network of roughly 100 billion neurons enables us to walk, talk and breathe, among hundreds of other essential activities of everyday life.²

When damage occurs and that network becomes compromised, neurofilaments are released into cerebrospinal fluid (CSF) and the bloodstream. Through numerous academic and industry studies, scientists now recognize that elevated levels of neurofilaments are associated with some of the most devastating neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and spinal muscular atrophy (SMA).^{3, 4, 5}

Neurofilaments are released into cerebrospinal fluid (CSF) and blood when neurons are damaged. Scientists are working to create more and more accurate tools (assays) to measure neurofilament in the blood.⁶

Looking into the future, biomarker panels, including neurofilaments, may be able to not only help identify these and other neurological conditions, but also potentially predict where the diseases are headed and how patients are responding to different therapies.

Biomarkers can answer many key questions that have a huge impact on the design, duration and probability of success in clinical trials. Who are the right patients? Is the drug impacting the relevant biological pathways? What are the proper doses and treatment periods? How far has the disease progressed? Does the treatment slow disease progression? ALS is one of the diseases where the use of neurofilament has helped answer some of these questions.

ALS researchers have found that levels of neurofilament have the potential to predict how the disease may progress and how long someone may survive.^7,8,9 Similar to what we see in SMA, we believe that lowering of neurofilament levels with a treatment in ALS may provide an early indication that disease progression is being slowed.^5,10

By answering these questions through biomarker testing, researchers can create more rigorous, well- controlled clinical trials that yield better data and richer scientific insights. Clinicians will be able to track treatment results more often, more rapidly and more accurately. The ultimate goal: accelerating drug development to get meaningful treatments to patients faster, giving greater hope to people and their families living with some of the most heart-wrenching diseases.

For complex brain diseases, treatment often starts with earlier identification. Here again, biomarkers can play a critical role. Through genetic testing, we can identify people at risk of neurodegenerative diseases. By monitoring neurofilament levels in people’s blood, clinical trials can identify individuals at-risk of neurodegenerative diseases earlier and potentially start them on treatments before they develop physical symptoms.¹¹

For example, the Foundation for the National Institutes of Health launched a project to identify the best blood test to assess the risk of Familial Frontotemporal Degeneration and ALS in people with genetic markers for the diseases (Biogen is one of 19 organizations participating in the project).¹²

This is exactly the kind of advancement that biomarkers have helped deliver for cancer patients. Numerous cancer biomarkers allow for earlier and more accurate identification of disease, and the ability to monitor disease progression or response to treatment. Using biomarkers, cancer specialists can now design treatment strategies tailored to individuals to ensure they are receiving the most effective combination of therapies – all to the benefit of patients.¹³

Over the last few decades, we have taken great steps towards a golden age in neuroscience. Advanced imaging technologies are enabling scientists and researchers to unlock the secrets of the brain by tracking brain activity over time. High- powered data analytics are helping to map neuron activity and provide insights into how neurodegenerative disease progress. Biomarkers, such as neurofilaments evaluated through simple blood tests, have the potential to help drive the next great advance and revolutionize our ability to diagnose, treat and monitor people with many devastating diseases.

Hear from the head of biomarkers at Biogen to learn more about the work we are doing in biomarkers.