A5054671725- Neuroinflammation and Neurodegeneration Mechanisms
- Multiple Sclerosis Research Studies
- Neurogenesis and neuroplasticity mechanisms
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immune cells in cancer
- Immune Response and Inflammation
- MicroRNA in disease regulation
- Immune Cell Function and Interaction
- Sphingolipid Metabolism and Signaling
- Peripheral Neuropathies and Disorders
- Amyotrophic Lateral Sclerosis Research
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Cell Adhesion Molecules Research
- Single-cell and spatial transcriptomics
- Neurogenetic and Muscular Disorders Research
- RNA regulation and disease
- Axon Guidance and Neuronal Signaling
- Systemic Lupus Erythematosus Research
- Polyomavirus and related diseases
- RNA Research and Splicing
- Barrier Structure and Function Studies
Montreal Neurological Institute and Hospital
2016-2025
McGill University
2016-2025
Institute of Neuroimmunology of the Slovak Academy of Sciences
1998-2021
McGill University Health Centre
2010-2020
University of Chicago Medical Center
1980-2020
Centre Hospitalier de l’Université de Montréal
2020
University of Duisburg-Essen
2019
Essen University Hospital
2019
NeuroRx Research (Canada)
2018
Vrije Universiteit Amsterdam
2018
There is increasing evidence that B lymphocytes are involved in the pathogenesis of multiple sclerosis, and they may be a therapeutic target. Rituximab, monoclonal antibody, selectively targets depletes CD20+ lymphocytes.In phase 2, double-blind, 48-week trial involving 104 patients with relapsing-remitting we assigned 69 to receive 1000 mg intravenous rituximab 35 placebo on days 1 15. The primary end point was total count gadolinium-enhancing lesions detected magnetic resonance imaging...
Fingolimod (FTY720) is a new oral immunomodulating agent under evaluation for the treatment of relapsing multiple sclerosis.We randomly assigned 281 patients to receive fingolimod, at dose 1.25 mg or 5.0 mg, placebo once daily, and we followed these 6 months with magnetic resonance imaging (MRI) clinical evaluations (core study, 0 6). The primary end point was total number gadolinium-enhanced lesions recorded on T(1)-weighted MRI monthly intervals months. In an extension study in which...
Rituximab, a monoclonal antibody selectively depleting CD20+ B cells, has demonstrated efficacy in reducing disease activity relapsing-remitting multiple sclerosis (MS). We evaluated rituximab adults with primary progressive MS (PPMS) through 96 weeks and safety 122 weeks.Using 2:1 randomization, 439 PPMS patients received two 1,000 mg intravenous or placebo infusions every 24 weeks, (4 courses). The endpoint was time to confirmed progression (CDP), prespecified increase Expanded Disability...
Impaired function/differentiation of progenitor cells might provide an explanation for the limited remyelination observed in majority chronic multiple sclerosis lesions. Here, we establish that normal adult human CNS, transcription factors Nkx2.2 and Olig2 are strongly expressed while mature oligodendrocytes characterized by low levels or Nkx2.2. In vitro studies confirmed expression oligodendroglial astrocytes, microglial neurons were negative Olig2. early lesions, found Olig2-positive...
We have developed a series of mouse-mouse neural hybrid cell lines by fusing the aminopterin-sensitive neuroblastoma N18TG2 with motor neuron-enriched embryonic day 12–14 spinal cord cells. Of 30 neuroblastoma-spinal (NSC) hybrids displaying multipolar neuron-like phenotype, 10 express choline acetyltransferase, and 4 induce twitching in cocultured mouse myotubules. NSC-19, NSC-34, their subclones additional properties expected neurons, including generation action potentials, expression...
Abstract The specific signals mediating the activation of microglia and astrocytes as a prelude to, or consequence of, CNS inflammation continue to be defined. We investigated TLRs novel receptors innate immune responses in human glial cells. find that express mRNA for 1–9, whereas robust TLR3, low-level TLR 1, 4, 5, 9, rare-to-undetectable 2, 6, 7, 8, 10 (quantitative real-time PCR). focused on 3 which can signal through both MyD88-dependent -independent pathways, MyD88-restricted TLR2. By...
The serum of most neuromyelitis optica (NMO) patients contains autoantibodies (NMO-IgGs) directed against the aquaporin-4 (AQP4) water channel located on astrocyte foot processes in perivessel and subpial areas brain. Our objectives were to determine source central nervous system (CNS) NMO-IgGs their role disease pathogenesis.Fluorescence-activated cell sorting single-cell reverse transcriptase polymerase chain reaction used identify overrepresented plasma immunoglobulin (Ig) sequences...
<h3>Objective</h3> To assess axonal damage and its contribution to disability at different stages of multiple sclerosis (MS). <h3>Background</h3> Recent in vivo imaging situ pathologic studies have demonstrated that substantial accompanies the inflammatory lesions MS. However, relation duration MS disease remain poorly defined. <h3>Design</h3> We performed proton magnetic resonance spectroscopic 88 patients with a wide range clinical measure<i>N</i>-acetylaspartate (NAA, an index integrity)...
It has been difficult to establish a strong correlation between total brain T2-weighted lesion volume on MRI and clinical disability in multiple sclerosis, part because of the lack pathological specificity signal changes. Proton magnetic resonance spectroscopy studies have shown that measurements intensity N-acetylaspartate (which is localized exclusively neurons neuronal processes mature brain) can provide specific index axonal damage or dysfunction. Here we report 30-month longitudinal...
Microglia are increasingly implicated in brain pathology, particularly neurodegenerative disease, with many genes Alzheimer's, Parkinson's, and motor neuron disease expressed microglia. There is, therefore, a need for authentic, efficient vitro models to study human microglial pathological mechanisms. originate from the yolk sac as MYB-independent macrophages, migrating into developing complete differentiation. Here, we recapitulate ontogeny by highly differentiation of embryonic...
Cancer stem cells are critical for cancer initiation, development, and treatment resistance. Our understanding of these processes, how they relate to glioblastoma heterogeneity, is limited. To overcome limitations, we performed single-cell RNA sequencing on 53586 adult 22637 normal human fetal brain cells, compared the lineage hierarchy developing transcriptome cells. We find a conserved neural tri-lineage centered around glial progenitor-like also that this progenitor population contains...
Abstract Both microglia, the resident myeloid cells of CNS parenchyma, and infiltrating blood‐derived macrophages participate in inflammatory responses CNS. Macrophages can be polarized into M1 M2 phenotypes, which have been linked to functional properties including production inflammation association molecules phagocytic activity. We compare phenotypic microglia derived from adult human with peripheral blood monocytes response polarizing conditions. Under conditions, upregulate expression...
Glioblastomas are highly infiltrated by diverse immune cells, including microglia, macrophages, and myeloid-derived suppressor cells (MDSCs). Understanding the mechanisms which glioblastoma-associated myeloid (GAMs) undergo metamorphosis into tumor-supportive characterizing heterogeneity of cell phenotypes within glioblastoma subtypes, discovering new targets can help design efficient immunotherapies. In this study, we performed a comprehensive battery phenotyping, whole-genome microarray...
<b>Objective:</b> To analyze and compare the extent of remyelination in lesions from patients with multiple sclerosis (MS) who have a short (early MS lesions) or long (chronic disease duration to determine influence anatomic localization on remyelination. In early lesions, has been described as relatively frequent event, contrast chronic where is absent limited lesion border majority lesions. However, no studies published that quantified compared <b>Methods:</b> We analyzed occurrence 52...