Advancing diagnosis and follow-up together

Given the limited therapeutic options for neurodegenerative diseases, researchers and industry are pooling their strengths to accelerate progress in diagnosis and treatment.

Doris Pischitz
Published on 5. Januar 2022

Laboratory diagnostics is a promising field that could help physicians arrive at an earlier diagnosis and facilitate monitoring and follow-up during treatment.

Today, biomarkers for neurodegenerative diseases are mainly detected in the lab by analyzing cerebrospinal fluid (CSF). Changes (compared to healthy individuals of the same age) in levels of beta-amyloid, total tau, and phosphorylated tau proteins are signs of Alzheimer’s disease and other causes of cognitive impairment , while α-synuclein protein points to Parkinson’s disease.[1] Measurements of neurofilament light chain (NfL) levels also help physicians assess a variety of inflammatory, neurodegenerative, traumatic, and cerebrovascular neurological disorders.[2] A lumbar puncture to draw CSF is, however, uncomfortable for the patient and expensive for the healthcare system. The procedure requires local anesthesia, 24 hours of rest, and in some cases even an overnight hospital stay. Punctures must also be repeated over the course of the disease to determine progression or treatment success. NfL testing is therefore increasingly being performed using more convenient blood samples.1

Cerebrospinal fluid is a clear liquid that surrounds the brain and spinal cord.

NfL is a protein contained in myelinated axons. Myelination can greatly increase the speed at which signals are transmitted between neurons.[3] Elevated levels of NfL in CSF are a sign of neuronal injury and the degeneration of these axons. Neuronal injury occurs in disease processes that affect both the central and peripheral nervous systems. The level of NfL increases in proportion to the degree of chronic axonal damage. The role of NfL has been studied in, for example, multiple sclerosis and Alzheimer’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, atypical parkinsoniandisorders, and traumatic brain injuries.[2] However, even under normal conditions, low levels of NfL are constantly released, with the amount probably depending on a person’s age.

An axon is a nerve fiber.

NfL is released when neuronal damage occurs.

NfL is a protein found in myelinated axons. Elevated levels of NfL in CSF and blood are a sign of neuronal injury. Source: Khalil M, Teunissen CE, Otto M, et al. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol. 2018;14(19):577–589.

Emerging evidence suggests NfL might be important in predicting the progression of multiple sclerosis (MS). MS patients with elevated levels of NfL were 40–70% more likely than those with low levels to have worsening symptoms within one year.[4] An additional study confirmed that patients with high NfL have more relapses, more active lesions on magnetic resonance imaging, a higher rate of brain volume loss (including gray matter), and a greater risk of long-term disability.[5]

Many MS medications are administered intravenously.

A patient receives an infusion.
To improve the diagnostic workup and support the development and monitoring of effective disease-modifying therapies, clinicians need easily accessible, cost-effective, and accurate blood-based tests for signs of neurodegeneration. At its Center for Innovation in Diagnostics (CID) CLIA laboratory in Berkeley, California, Siemens Healthineers already offers a range of tailored neurobiomarker testing services – including NfL in CSF, serum, and plasma – for drug development programs at biopharmaceutical companies. The NfL values generated from the assay have been shown to be associated with clinical and radiological measures of disease activity in patients with MS.

A master collaboration agreement with Novartis Pharma AG aims to design, develop, and commercialize diagnostic tests for therapeutic products across Novartis’ therapeutic pipeline. The initial program is supporting the development of a serum NfL (sNfL) immunoassay that runs on immunoassay platforms from Siemens Healthineers and is designed for use in clinical laboratories worldwide2. This will serve Novartis’ MS and other neuroscience programs. As a leading pharmaceutical company in neuroscience, Novartis is deeply committed to bringing transformative treatments to people suffering from neurological conditions such as MS, where there is a high level of unmet needs.

Easily accessible diagnosis is not only important for a patient’s inclusion in clinical trials of new medication. It can also be a prerequisite for initiating certain disease-modifying treatments once they have been approved – especially as the aim is for treatments to become more precisely targeted to the individual patient and the specific point in the course of their disease. With sNfL available as a routine test on clinical platforms, clinical laboratories should be able to offer these biomarker tests to patients with MS and other devastating neurological disorders.

By Doris Pischitz
Doris Pischitz is an editor in corporate communications at Siemens Healthineers. The team specializes in topics related to healthcare, medical technology, disease areas, and digitalization.