Multi-Omics Profiling of Cerebrospinal Fluid: A Strategy for Unveiling Multiple Sclerosis

Multiple sclerosis is an inflammatory and chronic disease of the central nervous system. It affects about 3 million people worldwide, primarily young patients, and unfortunately remains without a cure. Cerebrospinal fluid plays a key role in the diagnostic work-up, helping to reduce the chances of misdiagnosis, some of them caused by misinterpretation of neuroimaging results. The revision of the McDonald criteria in 2024 indicates two key parameters that must be evaluated in the cerebrospinal fluid of patients with multiple sclerosis, oligoclonal bands and the kappa index. Indeed, cerebrospinal fluid envelops various structures of the central nervous system and contains traces of proteins, immunoglobulins, and small molecules capable of crossing the blood-brain barrier, making it useful in clinical practice. Therefore, a multi-omics profiling of cerebrospinal fluid can contribute to the development of new diagnostic markers, as well as monitoring the therapeutic failure of disease-modifying drugs. It enables more targeted treatment, better outcomes for the patient, and a lower economic burden for funding organizations. This chapter intends to discuss the potential of different omics approaches and related technologies to identify biomarkers in cerebrospinal fluid.