Limited Benefits Halt Enrollment in Hematopoietic Stem Cell Transplantation Trial for Stiff-Person Syndrome DOI
Marinos C. Dalakas

Neurology, Journal Year: 2020, Volume and Issue: 96(6), P. 239 - 240

Published: Dec. 16, 2020

Stiff-person syndrome (SPS) is an autoimmune disease characterized by stiffness of truncal and proximal limb muscles due to co-contracture agonist antagonist resulting in hyperlordosis, difficulty bending, slow gait, statue-like appearance; episodic spasms precipitated unexpected auditory, tactile, visual, or stressful stimuli; task-specific phobias.1,2 High-titer autoantibodies against glutamic acid decarboxylase (GAD)–65, the rate-limiting enzyme for GABA synthesis, glycine receptors are detected most patients, denoting impaired inhibitory neurotransmission causing excitotoxicity, spasms, stiffness.1–3 High GAD titers also seen, overlap with, epilepsy, encephalitis, cerebellar ataxia, myoclonus, forming spectrum disorder.2,3 SPS responds GABA-enhancing drugs (diazepam, baclofen, anticonvulsants) certain immunotherapies.1–4 A placebo-controlled trial with IV immunoglobulin (IVIg) showed significant improvements 70% patients,5 but a randomized controlled rituximab did not reach significance strong placebo effect, although 35% patients improved.6 Plasmapheresis, corticosteroids, immunosuppressants variably show limited benefits.2–4 Patients poorly responding these therapies may become permanently impaired, requiring walkers wheelchairs. Additional immunotherapies therefore welcome.

Language: Английский

Bone marrow hematopoiesis drives multiple sclerosis progression DOI Creative Commons
Kaibin Shi, Handong Li, Ting Chang

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(13), P. 2234 - 2247.e17

Published: June 1, 2022

Multiple sclerosis (MS) is a T cell-mediated autoimmune disease of the central nervous system (CNS). Bone marrow hematopoietic stem and progenitor cells (HSPCs) rapidly sense immune activation, yet their potential interplay with autoreactive in MS unknown. Here, we report that bone HSPCs are skewed toward myeloid lineage concomitant clonal expansion patients. Lineage tracing experimental encephalomyelitis, mouse model MS, reveals remarkable myelopoiesis an augmented output neutrophils Ly6Chigh monocytes invade CNS. We found myelin-reactive preferentially migrate into compartment CXCR4-dependent manner. This aberrant involves CCL5-CCR5 axis augments CNS inflammation demyelination. Our study suggests targeting niche presents avenue to treat other disorders.

Language: Английский

Citations

88
High-Efficacy Therapies for Treatment-Naïve Individuals with Relapsing–Remitting Multiple Sclerosis DOI Creative Commons
Léorah Freeman, Erin E. Longbrake, Patricia K. Coyle

et al.

CNS Drugs, Journal Year: 2022, Volume and Issue: 36(12), P. 1285 - 1299

Published: Nov. 9, 2022

There are > 18 distinct disease-modifying therapy (DMT) options covering 10 mechanisms of action currently approved by the US Food and Drug Administration for treatment relapsing-remitting multiple sclerosis (RRMS). Given multitude available options, recent international consensus guidelines offering differing recommendations, there is broad heterogeneity in how DMTs used clinical practice. Choosing a DMT newly diagnosed patients with MS topic significant debate care. Historically, an escalation approach to was RRMS. However, evidence benefits early high-efficacy therapies (HETs) this population emerging. In review, we provide overview strategies, discuss HETs (including ofatumumab, ocrelizumab, natalizumab, alemtuzumab, cladribine) stages MS, along safety concerns associated these DMTs. By minimizing accumulation neurological damage disease course, may enhance long-term outcomes over lifetime patient.

Language: Английский

Citations

76
Multiple sclerosis: time for early treatment with high-efficacy drugs DOI Creative Commons
Krzysztof Selmaj, Bruce Cree, Michael Barnett

et al.

Journal of Neurology, Journal Year: 2023, Volume and Issue: 271(1), P. 105 - 115

Published: Oct. 18, 2023

Abstract This review addresses current changes in the approach to treating patients with multiple sclerosis (MS). The widely practiced of utilizing agents lower treatment efficacy (LETA) at onset subsequent escalation has been challenged by new data suggesting that MS derive greater benefit when therapy is initiated high-efficacy (HETA). Several recent studies compared and safety early administration HETA versus LETA. results randomized, double blind, phase III LETA as a control arm population-based larger longer using propensity scoring, marginal structural modeling weighted cumulative exposure analysis support HETA. Patients initiating their HETA, regardless prognostic factors MRI burden baseline, showed significantly annualized relapse rate (ARR) reduced disability progression follow-up periods up 10–15 years. Moreover, profile recently approved ameliorates concerns about off-target effects associated number earlier drugs. Patient perception also changed an increasing preference for medication profiles both improve symptoms prevent disease progression. Accumulating from randomized large demonstrating short-term longer-term patient benefits view should be more used. adoption capitalizes on window opportunity anti-inflammatory drugs maximally impact pathology heralds sea change clinical practice toward pro-active management away philosophy routed generating consequence failure.

Language: Английский

Citations

27
Advances in clinical translation of stem cell-based therapy in neurological diseases DOI
Yu Wang,

Yirong Cao,

Wanqing Xie

et al.

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Stem cell-based therapies have raised considerable interest to develop regenerative treatment for neurological disorders with high disability. In this review, we focus on recent preclinical and clinical evidence of stem cell therapy in the degenerative diseases discuss different types, delivery routes biodistribution therapy. addition, advances mechanistic insights therapy, including functional replacement by exogenous cells, immunomodulation paracrine effects are also demonstrated. Finally, highlight adjunction approaches that has been implemented augment their reparative function, survival migration target specific tissue, preconditioning, genetical engineering, co-transplantation combined

Language: Английский

Citations

1
Cumulative Roles for Epstein-Barr Virus, Human Endogenous Retroviruses, and Human Herpes Virus-6 in Driving an Inflammatory Cascade Underlying MS Pathogenesis DOI Creative Commons
Ute‐Christiane Meier,

Richard Christopher Cipian,

Abbas Karimi

et al.

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Nov. 1, 2021

Roles for viral infections and aberrant immune responses in driving localized neuroinflammation neurodegeneration multiple sclerosis (MS) are the focus of intense research. Epstein-Barr virus (EBV), as a persistent frequently reactivating with major immunogenic influences near 100% epidemiological association MS, is considered to play leading role MS pathogenesis, triggering inflammation or within central nervous system (CNS). This may occur directly via products (RNA protein) and/or indirectly antigenic mimicry involving B-cells, T-cells cytokine-activated astrocytes microglia cells damaging myelin sheath neurons. The genetic MS-risk factor HLA-DR2b (DRB1*1501β, DRA1*0101α) contribute EBV antigen-presentation anti-EBV reactivity but also mimicry-induced autoimmune characteristic MS. A proposed inflammatory EBER1, EBV-miRNA LMP1 containing exosomes secreted by viable EBV+ B-cells repetitive release EBNA1-DNA complexes from apoptotic forming reactive EBNA1-IgG complement. be accompanied cytokine- EBV-induced expression human endogenous retrovirus-W/-K (HERV-W/-K) elements possibly activation herpesvirus-6A (HHV-6A) early-stage CNS lesions, each contributing an cascade causing relapsing-remitting neuro-inflammatory progressive features Elimination EBV-carrying antibody- EBV-specific T-cell therapy hold promise reducing activity CNS, thereby limiting inflammation, symptoms reversing disease. Other approaches targeting HHV-6 HERV-W kinase-signaling treat being tested promising results. article presents overview evidence that EBV, HHV-6, have pathogenic initiating promoting possible mitigate development

Language: Английский

Citations

49
The American stem cell sell in 2021: U.S. businesses selling unlicensed and unproven stem cell interventions DOI Creative Commons
Leigh Turner

Cell stem cell, Journal Year: 2021, Volume and Issue: 28(11), P. 1891 - 1895

Published: Nov. 1, 2021

Language: Английский

Citations

44
The risk of infections for multiple sclerosis and neuromyelitis optica spectrum disorder disease-modifying treatments: Eighth European Committee for Treatment and Research in Multiple Sclerosis Focused Workshop Review. April 2021 DOI
Carmen Tur, Anne‐Laure Dubessy, Susana Otero‐Romero

et al.

Multiple Sclerosis Journal, Journal Year: 2022, Volume and Issue: 28(9), P. 1424 - 1456

Published: Feb. 23, 2022

Over the recent years, treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has evolved very rapidly a large number disease-modifying treatments (DMTs) are now available. However, most DMTs associated with adverse events, frequent which being infections. Consideration all DMT-associated risks facilitates development risk mitigation strategies. An international focused workshop expert-led discussions was sponsored by European Committee for Treatment Research in Multiple Sclerosis (ECTRIMS) held April 2021 to review our current knowledge about infections use people MS NMOSD corresponding The addressed specific populations, such as children pregnant women MS, or who have other comorbidities live regions an exceptionally high infection burden. Finally, we reviewed topic infectious context SARS-CoV-2 pandemic. Herein, summarize available evidence identify gaps justify further research.

Language: Английский

Citations

34
Multiple Sclerosis Pathogenesis and Updates in Targeted Therapeutic Approaches DOI
Eleni S. Vasileiou, Kathryn C. Fitzgerald

Current Allergy and Asthma Reports, Journal Year: 2023, Volume and Issue: 23(9), P. 481 - 496

Published: July 4, 2023

Language: Английский

Citations

19
Myeloid cell replacement is neuroprotective in chronic experimental autoimmune encephalomyelitis DOI
Marius Marc-Daniel Mader,

Alan Napole,

Danwei Wu

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(5), P. 901 - 912

Published: March 21, 2024

Language: Английский

Citations

6
Stem Cell Therapies for Progressive Multiple Sclerosis DOI Creative Commons
Jayden A. Smith, Alexandra M. Nicaise, Rosana-Bristena Ionescu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: July 9, 2021

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination and axonal degeneration. MS patients typically present with relapsing-remitting (RR) course, manifesting as sporadic attacks neurological symptoms including ataxia, fatigue, sensory impairment. While there are several effective disease-modifying therapies able to address relapses associated RRMS, most will inevitably advance progressive course marked gradual irreversible accrual disabilities. Therapeutic intervention in (PMS) suffers from lack well-characterized biological targets and, hence, dearth successful drugs. The few medications approved for treatment PMS limited their efficacy active forms disease, have little impact on slowing degeneration, fail promote repair. In looking these unmet needs, multifactorial therapeutic benefits stem cell particularly compelling. Ostensibly providing neurotrophic support, immunomodulation replacement, transplantation holds substantial promise combatting complex pathology neuroinflammation. Herein, we explore current state preclinical clinical evidence supporting use cells treating discuss prospective hurdles impeding translation into revolutionary regenerative medicines.

Language: Английский

Citations

37