Exploiting Biomarkers of CNS Disorders: Targets for Therapeutics and Non-Invasive Tools for Diagnosis, Prognosis, Monitoring

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Background

The Central Nervous System (CNS) organizes, initiates, and coordinates physical and mental actions. Movement and cognition can be compromised due to CNS dysregulation, which disrupts physical and cognitive functions and emotional well-being.
Patients with neurological disorders are more prone to psychiatric conditions, such as mood swings, depression, social withdrawal, and psychosis. Conversely, many mental illnesses also manifest with somatic symptoms.

CNS disorders include infections, degeneration, structural defects, trauma, tumors, and autoimmune disorders, affecting one-sixth of the world's population. Despite the efforts, CNS disease management is still a great challenge because of insufficient knowledge of the underlying mechanisms, late diagnosis, and lack of effective treatment. Identification and sensitive detection of specific biomarkers, including those detectable in the peripheral circulation, represents a game-changer in early diagnosis and may lead to more efficacious treatments and better outcomes.

Hence, lately, there has been a growing interest in developing and validating new biomarker candidates for CNS pathologies supported by federal agencies around the world, focusing attention on neurological biomarkers, their context of use, and their clinical validation.
For example, recently, FDA approved Tauvid (flortaucipir F18) to be used in PET imaging, the first compound to aid in visualizing tau pathology, a defining feature of Alzheimer's disease (AD). Moreover, Lumipulse G, approved by the FDA this year, is the first in vitro test for the early diagnosis of AD monitored by the dysregulation of amyloid plaque ratio. These newly available innovative tests pave the way for developing and further applying novel biomarkers currently being developed for many other CNS diseases.

Many genetic, neurofilament, and immune-related biomarkers previously explored for CNS diseases have limited utility for diagnosis. There is therefore an urgent need to develop new biomarkers, particularly non-invasive or minimally invasive biofluid biomarkers, e.g., blood or urine for clinical use. For instance, the emerging blood biomarker Treg cells, correlates with a good prognosis and is being considered a promising therapeutic target, and the urinary neurotrophin receptor p75ECD is a good indicator of the presence and progression of ALS. In neurodegenerative proteinopathies, the ability to measure seed amplification, e.g., of α-synuclein, in CNS-originating extracellular vesicles isolated from the blood is a promising approach. Other noninvasive neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) have been instrumental in improving our understanding of the effect of CNS pathologies on brain networks. The network changes detected by these imaging techniques may become neuroimaging biomarkers for early diagnosis of these diseases. Nevertheless, to date, our CNS diseases biomarkers armamentarium remains limited, and there is a dire need to expand it to improve therapeutic approaches and provide insights into the neuropathophysiology that in turn, aids in our approach toward more efficient and selective therapies for brain and spinal cord diseases.

Based on the BEST classification, biomarker categories according to their clinical use are defined as diagnostic, monitoring, prognostic, predictive, pharmacodynamic/response, susceptibility/risk, and safety. There are many factors that must be considered when determining the biomarker purpose, such as the type (e.g., molecular, histological, radiographic, physiological), distribution, half-life period, and/or detection challenges, along with its reliability in discerning pathophysiological processes.

Molecular, cellular, structural, or functional pathologic indicators are crucial for diagnosing, predicting prognosis, and monitoring disease progression. Biomarkers and biomarkers signatures may also be valuable assets in evaluating the response to therapeutic intervention and designing effective therapeutic strategies. In addition to this, reliable biomarker traceability and predictive statistical modeling approaches will be particularly conducive to performing an accurate analysis of treatment efficacy relying on an expanding collection of multiple available datasets.

Biomarkers also are highly important for disentangling the underlying disease mechanisms and ultimately provide the tools necessary to enable the clinical development of neurotherapeutics, treating effectively neurodegenerative diseases and other CNS conditions, including AD, Parkinson’s (PD), amyotrophic lateral sclerosis (ALS), stroke, cancer, traumatic injuries, neoplasm, and neuroimmune disorders.

This Research Topic intends to account for the characteristic alterations of the CNS inherent to the main neurological and neuropsychiatric disorders with a focus on recent advances in CNS biomarkers discovery and translational usage.

We welcome articles focusing on biological markers featuring CNS disorders and addressing the following:

- Pathological markers of CNS disorders, including neurological and neuropsychiatric disorders
- Biomarkers for early detection of brain and/or spinal cord impairment
- Diagnostic biomarkers to identify the clinical manifestation of the disease
- Prognostic biomarkers for determining outcomes
- Monitoring and treatment-predictive biomarkers to track disease progression and successful responders
- Eliciting pathophysiological mechanisms in CNS dysfunction and potential therapeutic targets
- Biomarker validation and response
- Novel technologies for sensitive and accurate identification and/or tracking of biological markers.
- Innovative approaches to amplify and/or accelerate biomarker discovery.

Keywords: biomarkers, CNS, translational, brain impairment, spinal cord impairment, prognostic biomarker, AD, PD, ALS

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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