Biomarkers of Progression Independent of Relapse Activity—Can We Actually Measure It Yet? DOI Open Access
Gabriel Bsteh, Assunta Dal‐Bianco, Nik Krajnc

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(10), С. 4704 - 4704

Опубликована: Май 14, 2025

Progression independent of relapse activity (PIRA) is increasingly recognized as a key driver disability in multiple sclerosis (MS). However, the concept PIRA remains elusive, with uncertainty surrounding its definition, underlying mechanisms, and methods quantification. This review examines current landscape biomarkers used to predict measure PIRA, focusing on clinical, imaging, body fluid biomarkers. Clinical scores such Expanded Disability Status Scale (EDSS) are widely used, but may lack sensitivity capturing subtle relapse-independent progression. Imaging biomarkers, including MRI-derived metrics (brain spinal cord volume loss, chronic active lesions) optical coherence tomography (OCT) parameters (retinal nerve fiber layer ganglion cell-inner plexiform thinning), offer valuable insights, often reflect both inflammatory neurodegenerative processes. Body neurofilament light chain (NfL) glial fibrillary acidic protein (GFAP), promising indicators axonal damage activation, their specificity for limited. emphasizes distinction between predicting PIRA-identifying individuals at risk future progression-and measuring ongoing PIRA-related real time. We highlight limitations differentiating from relapse-associated call clearer conceptual framework guide research. Advancing precision utility will require multimodal approaches, longitudinal studies, standardized protocols enable clinical integration improve personalized MS management.

Язык: Английский

Quantitative myelin imaging with MRI and PET: an overview of techniques and their validation status DOI Creative Commons
Chris W.J. van der Weijden, Emma Biondetti,

Ingomar W. Gutmann

и другие.

Brain, Год журнала: 2022, Номер 146(4), С. 1243 - 1266

Опубликована: Ноя. 18, 2022

Myelin is the protective sheath wrapped around axons, consisting of a phospholipid bilayer with water between wraps. The measurement damage to myelin sheaths, evaluation efficacy therapies aiming promote remyelination and monitoring degree brain maturation in children all require non-invasive quantitative imaging methods. To date, various techniques have been developed. Five different MRI approaches can be distinguished based on their biophysical principles: (i) lipid bilayers directly (e.g. imaging); (ii) non-aqueous protons ultra-short echo-time techniques; (iii) indirect macromolecular content magnetization transfer; inhomogeneous transfer); (iv) mapping effects sheath's magnetic susceptibility signal mapping); (v) diffusion. PET uses radioactive molecules high affinity specific components, particular basic protein. This review aims give an overview techniques, principles, image acquisition, data analysis validation status.

Язык: Английский

Процитировано

39
Microglia in multiple sclerosis – pathogenesis and imaging DOI
Laura Airas, V. Wee Yong

Current Opinion in Neurology, Год журнала: 2022, Номер 35(3), С. 299 - 306

Опубликована: Июнь 1, 2022

Purpose of review Microglia normally protects the central nervous system (CNS) against insults. However, their persistent activation in multiple sclerosis (MS) contributes to injury. Here, we microglia MS and detection using positron emission tomography (PET). Recent findings During lesion evolution progression MS, activity may contribute neurotoxicity through release pro-inflammatory cytokines, reactive oxidative species, proteases glutamate. A means detect monitor individuals living with is provided by (PET) imaging mitochondrial 18-kDa translocator protein (TSPO) ligand. TSPO PET shows increased microglial within normal appearing white matter that precedes radiological signs neurodegeneration measured T2 enlargement. PET-detected increases MS. These demand use CNS penetrant inhibitors affect microglia. Such therapies include hydroxychloroquine recently reported a small study reduce expected primary progressive Bruton's tyrosine kinase for which there are now eleven Phase 3 registered trials Summary Microglial drives injury microglia-specific ligands offer new insights into as treatment responses.

Язык: Английский

Процитировано

37
Assessing disease progression and treatment response in progressive multiple sclerosis DOI
Gıancarlo Comı, Gloria Dalla Costa, Bruno Stankoff

и другие.

Nature Reviews Neurology, Год журнала: 2024, Номер 20(10), С. 573 - 586

Опубликована: Сен. 9, 2024

Язык: Английский

Процитировано

8
Immune mechanisms and shared immune targets in neurodegenerative diseases DOI
Howard L. Weiner

Nature Reviews Neurology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 16, 2024

Язык: Английский

Процитировано

8
General In Situ Engineering of Carbon‐Based Materials on Carbon Fiber for In Vivo Neurochemical Sensing DOI
Hui Zeng,

Guoyuan Ren,

Nan Gao

и другие.

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(36)

Опубликована: Июнь 20, 2024

Developing real-time, dynamic, and in situ analytical methods with high spatial temporal resolutions is crucial for exploring biochemical processes the brain. Although vivo electrochemical based on carbon fiber (CF) microelectrodes are effective monitoring neurochemical dynamics during physiological pathological processes, complex post modification hinders large-scale productions widespread neuroscience applications. Herein, we develop a general strategy engineering of carbon-based materials to mass-produce functional CFs by introducing polydopamine anchor zeolitic imidazolate frameworks as precursors, followed one-step pyrolysis. This demonstrates exceptional universality design flexibility, overcoming post-modification procedures avoiding delamination layer. simplifies fabrication integration CF-based microelectrodes. Moreover, highly stable selective H

Язык: Английский

Процитировано

7
The protein kinase C modulator bryostatin-1 therapeutically targets microglia to attenuate neuroinflammation and promote remyelination DOI
Payam Gharibani, Efrat Abramson, Shruthi Shanmukha

и другие.

Science Translational Medicine, Год журнала: 2025, Номер 17(780)

Опубликована: Янв. 8, 2025

In multiple sclerosis (MS), microglia and macrophages within the central nervous system (CNS) play an important role in determining balance among demyelination, neurodegeneration, myelin repair. Phagocytic regenerative functions of these CNS innate immune cells support remyelination, whereas chronic maladaptive inflammatory activation promotes lesion expansion disability, particularly progressive forms MS. No currently approved drugs convincingly target CNS, contributing to lack therapies aimed at promoting remyelination slowing disease progression for individuals with Here, we found that protein kinase C (PKC)–modulating drug bryostatin-1 (bryo-1), a CNS-penetrant compound established human safety profile, shifts transcriptional programs CNS-associated from proinflammatory phenotype vitro vivo. Treatment bryo-1 stimulated scavenger pathways, phagocytosis, secretion factors prevented neuroinflammatory reactive astrocytes while also neuroaxonal health oligodendrocyte differentiation. line findings, systemic treatment mice augmented after focal demyelinating injury. Our results demonstrate potential possibly wider class PKC modulators as myelin-regenerative supportive agents MS other neurologic diseases.

Язык: Английский

Процитировано

1
Identifying Biomarkers for Remyelination and Recovery in Multiple Sclerosis: A Measure of Progress DOI Creative Commons
Vito A. G. Ricigliano, Silvia Marenna, Serena Borrelli

и другие.

Biomedicines, Год журнала: 2025, Номер 13(2), С. 357 - 357

Опубликована: Фев. 4, 2025

Background: Multiple sclerosis (MS) pathology is characterized by acute and chronic inflammation, demyelination, axonal injury, neurodegeneration. After decades of research into MS-related degeneration, recent efforts have shifted toward recovery the prevention further damage. A key area focus remyelination process, where researchers are studying effects pharmacotherapy on myelin repair mechanisms. compounds being tested for their potential to foster in different clinical settings through application less or more complex techniques assess efficacy. Objective: To review current methods biomarkers track regeneration over time people with MS (PwMS), implications promyelinating drug testing. Methods: Narrative review, based a selection PubMed articles discussing measure vivo functional PwMS. Results: Non-invasive tools, such as structural Magnetic Resonance Imaging (MRI) Positron Emission Tomography (PET), implemented repair, while other like evoked potentials, MRI, digital markers allow assessment recovery. These methods, alone combination, been employed obtain precise various trials MS. Conclusions: Combining identify restoration could yield novel biomarkers, enhancing accuracy trial outcomes remyelinating therapies

Язык: Английский

Процитировано

1
PET imaging of reactive astrocytes in neurological disorders DOI Creative Commons
Yi Liu, Han Jiang,

Xiyi Qin

и другие.

European Journal of Nuclear Medicine and Molecular Imaging, Год журнала: 2021, Номер 49(4), С. 1275 - 1287

Опубликована: Дек. 7, 2021

Abstract The reactive astrocytes manifest molecular, structural, and functional remodeling in injury, infection, or diseases of the CNS, which play a critical role pathological mechanism neurological diseases. A growing need exists for dependable approach to better characterize activation astrocyte vivo. As an advanced molecular imaging technology, positron emission tomography (PET) has potential visualizing biological activities at cellular levels. In review, we summarized PET visualization strategies discussed applications Future studies are needed pay more attention development specific agents further improve our exploration various

Язык: Английский

Процитировано

24
Cognitive performance in multiple sclerosis: what is the role of the gamma-aminobutyric acid system? DOI Creative Commons
Marijn Huiskamp, Maqsood Yaqub, M R van Lingen

и другие.

Brain Communications, Год журнала: 2023, Номер 5(3)

Опубликована: Янв. 1, 2023

Abstract Cognitive impairment occurs in 40–65% of persons with multiple sclerosis and may be related to alterations glutamatergic GABAergic neurotransmission. Therefore, the aim this study was determine how changes relate cognitive functioning vivo. Sixty (mean age 45.5 ± 9.6 years, 48 females, 51 relapsing-remitting sclerosis) 22 age-matched healthy controls (45.6 22.0 17 females) underwent neuropsychological testing MRI. Persons were classified as cognitively impaired when scoring at least 1.5 standard deviations below normative scores on ≥30% tests. Glutamate GABA concentrations determined right hippocampus bilateral thalamus using magnetic resonance spectroscopy. GABA-receptor density assessed quantitative [11C]flumazenil positron emission tomography a subset participants. Positron outcome measures influx rate constant (a measure predominantly reflecting perfusion) volume distribution, which is density. Twenty (33%) fulfilled criteria for impairment. No differences observed glutamate or between controls, preserved, control groups. Twenty-two (12 preserved 10 impaired) successfully tomography. showed lower thalamus, indicating perfusion. For higher values than deep grey matter, increased When comparing patients group significantly distribution cortical matter hippocampus. Positive correlations both information processing speed only. Whereas did not differ nor impaired, groups, that seen patients. In addition, correlated cognition, particular speed. This could indicate upregulated phase means regulate neurotransmission potentially preserve functioning.

Язык: Английский

Процитировано

11
Choroid plexuses at the interface of peripheral immunity and tissue repair in multiple sclerosis DOI
Vito A. G. Ricigliano, Bruno Stankoff

Current Opinion in Neurology, Год журнала: 2023, Номер 36(3), С. 214 - 221

Опубликована: Апрель 17, 2023

Purpose of review Choroid plexuses (ChPs) are key actors the blood-to-cerebrospinal-fluid barrier and serve as brain immune checkpoint. The past years have seen a regain interest about their potential involvement in physiopathology neuroinflammatory disorders like multiple sclerosis (MS). This article offers an overview recent findings on ChP alterations MS, with focus imaging tools able to detect these abnormalities inflammation, tissue damage repair. Recent On MRI, ChPs enlarged people MS (PwMS) versus healthy individuals. size increase is early event, already detected presymptomatic pediatric MS. Enlargement linked local inflammatory infiltrates, dysfunction selectively impacts periventricular damage, larger predicting expansion chronic active lesions, smoldering inflammation remyelination failure tissues surrounding ventricles. volumetry may add value for prediction disease activity disability worsening. Summary metrics emerging possible biomarkers neuroinflammation repair Future works combining multimodal techniques should provide more refined characterization functional changes, link blood cerebrospinal-fluid fluid trafficking

Язык: Английский

Процитировано

10