Next Generation Biomarkers for Progressive Multiple Sclerosis
Principal Investigator: Peter Calabresi, M.D.
This study aims to identify markers of disease progression in multiple sclerosis that can be measured by a blood test.
Why is this study important?
Multiple sclerosis (MS) affects millions of people worldwide and is the most common non-traumatic cause of disability in young adults. MS can present as relapsing, with periodic acute attacks called relapses, or as progressive, with continuous gradual decline due to uncertain causes. How MS progresses, especially in the progressive form, is not well understood, and current biomarkers are not sensitive or practical enough to capture gradual MS progression. The current “gold standard” for measuring disability in MS is the EDSS, a standardized neurological exam. It is helpful but has many limitations, such as low sensitivity to change, examiner subjectivity, and over-emphasis of walking ability while downplaying other important MS symptoms. Better ways of measuring MS disease progression are needed to help doctors predict and detect early disease progression, and help researchers develop and measure the effectiveness of new treatments.
What are the study’s goals?
Goal 1:
This study will identify and evaluate markers of non-inflammatory disease progression for MS that can be quantified via blood test. This will be helpful for clinical and research usage, as well as potentially provide information about the mechanisms of MS.
Goal 2:
These blood markers will be further characterized to make them ready for clinical application, including by comparison to a non-MS reference population. This will allow us to better understand how the blood markers vary by age and other factors outside of MS.
What are biomarkers?
Biological markers (biomarkers) are measurements collected from an individual that indicate the status of a medical condition. Current biomarkers used for MS diagnosis, prognosis, and monitoring are measured from cerebrospinal fluid (CSF, the fluid in and around the brain and spinal cord) samples and magnetic resonance imaging (MRI) of the brain and spinal cord. However, they are not specific for MS and can signify other neurological disorders. They also are not sensitive enough to effectively measure disease progression. To address this issue, this study is looking to identify and validate new and emerging biomarkers from blood samples that indicate whether or not disease progression in MS is occurring.
What do we know so far?
An emerging biomarker for neuronal injury is neurofilament light (NfL). This is a cytoskeletal protein unique to neurons that structures the cell and shapes the axon. In MS, after immune cells cause damage to neurons, intracellular products including NfL leak out from damaged cells into the CSF and then into the blood stream. Another potential biomarker is glial fibrillary acid protein (GFAP), a structural protein key in astrocytes, a type of neural support cell, may be released during various types of neuronal stress as well. Because of this, measuring NfL, GFAP, or other intra-cellular contents in blood may be useful biomarkers for MS and will be measured annually in this study. In addition, we are using a technique called flow cytometry to look at circulating immune cells as well as examining extracellular vesicle, which are parts of cells that come out of the cell but carry cargo to facilitate communication between the brain and blood system.
What is the study’s timeline?
In this study, participants will include both volunteers with and without MS. Participating volunteers in this study will be followed for 5 years and have annual blood draws. Besides blood draws, volunteers without MS are asked questions about their demographics and medical history. For participants with MS, we will examine how their blood biomarkers correspond to many other important measures, such as imaging of the brain and spinal cord, optical coherence tomography (“OCT,” a measurement of retinal thickness), patient-reported outcomes, examination measurements like walking speed and EDSS, and cognitive tests.
