A5010771032- Multiple Sclerosis Research Studies
- Chronic Lymphocytic Leukemia Research
- Polyomavirus and related diseases
- Acute Lymphoblastic Leukemia research
- Systemic Lupus Erythematosus Research
- Fungal Plant Pathogen Control
- Chronic Myeloid Leukemia Treatments
- Lymphoma Diagnosis and Treatment
- Histone Deacetylase Inhibitors Research
- Peripheral Neuropathies and Disorders
- Immunotherapy and Immune Responses
- Cytokine Signaling Pathways and Interactions
- Mycobacterium research and diagnosis
- Systemic Sclerosis and Related Diseases
- Viral Infections and Immunology Research
- T-cell and Retrovirus Studies
- T-cell and B-cell Immunology
- Protein Degradation and Inhibitors
- RNA regulation and disease
- Monoclonal and Polyclonal Antibodies Research
- Immunodeficiency and Autoimmune Disorders
- Autoimmune Bullous Skin Diseases
- Cancer Treatment and Pharmacology
- Multiple Myeloma Research and Treatments
- CNS Lymphoma Diagnosis and Treatment
Research & Development Institute
2018-2022
Ono Pharmaceutical (United States)
2013-2022
Merck (Germany)
2014-2021
Merck Serono (Italy)
2013-2020
Therapeutics Clinical Research
2019
Ibero American University
2019
Center for Global Development
2019
Northwestern University
2018
Vanderbilt University Medical Center
2018
St. Michael's Hospital
2018
This study creates a compendium of gene expression in normal human tissues suitable as reference for defining basic organ systems biology. Using oligonucleotide microarrays, we analyze 59 samples representing 19 distinct tissue types. Of ∼7,000 genes analyzed, 451 are expressed all types and designated housekeeping genes. These display significant variation levels among sufficient discerning tissue-specific signatures, indicative fundamental differences biochemical processes. In addition,...
Resting autoreactive T cells are present in the circulation of normal individuals without pathologic consequences. In autoimmune animal models, stimulation these self-reactive presence costimulatory molecules B7-1 results cell-mediated disease, whereas B7-2 generates regulatory that abrogate disease severity. Thus, reactivation brain myelin-autoreactive by antigen with may be a critical event pathophysiology multiple sclerosis (MS), putative central nervous system (CNS) myelin. We...
Abstract Multiple molecular defects trigger cell death in amyotrophic lateral sclerosis (ALS). Among these, altered transcriptional activity may perturb many cellular functions, leading to a cascade of secondary pathological effects. We showed that pharmacological treatment, using the histone deacetylase inhibitor sodium phenylbutyrate, significantly extended survival and improved both clinical neuropathological phenotypes G93A transgenic ALS mice. Phenylbutyrate administration ameliorated...
Background: In the 2-year CLARITY study, cladribine tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing–remitting multiple sclerosis (MS). Objective: To assess safety efficacy of treatment a Extension study. Methods: this placebo recipients from received 3.5 mg/kg; were re-randomized 2:1 to mg/kg or placebo, blind maintained. Results: A total 806 assigned treatment. Adverse event rates generally similar between groups,...
Bruton's tyrosine kinase (BTK) regulates the functions of B cells and myeloid that are implicated in pathogenesis multiple sclerosis. Evobrutinib is a selective oral BTK inhibitor has been shown to inhibit B-cell activation both vitro vivo.
Immune reconstitution therapies (IRT) for patients with multiple sclerosis are used short, intermittent treatment periods to induce immune resetting and allow subsequent treatment-free periods. Cladribine tablets postulated be an IRT that causes selective transient reductions in CD19+ B cells T cells, followed by of adaptive function.To characterize long-term lymphocyte count changes pooled data from the 2-year CLARITY Extension studies, PREMIERE registry (Long-term cohort).Data randomized...
Cladribine tablets 3.5 mg/kg cumulative over 2 years (CT3.5) had significant clinical/imaging effects in patients with clinically isolated syndrome (CIS; ORACLE-MS) or relapsing-remitting MS (RRMS; CLARITY and Extension). This analysis compared the effect of cladribine on dynamics immune cell reduction reconstitution ORACLE-MS, CLARITY, Extension during first year treatment (i.e. course CT1.75) randomized to CT3.5.Lymphocyte subtypes were analyzed using multiparameter flow cytometry. Changes...
Little is known about global gene expression patterns in the human neurodegenerative disease amyotrophic lateral sclerosis (ALS). To address this, we used high-density oligonucleotide microarray technology to compare levels of ∼6,800 genes postmortem spinal cord gray matter obtained from individuals with ALS as well normal individuals. Using Fisher discriminant analysis (FDA) and leave-one-out cross-validation (LOOCV), discerned an ALS-specific signature. Moreover, it was possible...
To effectively direct targeted repression, the class I histone deacetylases (HDACs) associate with many important regulatory proteins. In this paper we describe molecular characterization of a member Jumonji domain 2 (JMJD2) family proteins, and demonstrate its binding to both HDACs retinoblastoma protein (pRb). JMJD2 proteins are characterized by presence two leukemia-associated protein/plant homeodomain (LAP/PHD) zinc fingers, one JmjN, JmjC (containing an internal retinoblastoma-binding...
Background: Neuroimaging studies have used magnetic resonance imaging-derived methods to assess brain volume loss in multiple sclerosis (MS) as a reliable measure of diffuse tissue damage. Methods: In the CLARITY study ( ClinicalTrials.gov NCT00213135), effect 2 years’ treatment with cladribine tablets on annualized percentage change (PBVC/y) was evaluated patients relapsing MS (RMS). Results: Compared placebo (–0.70% ± 0.79), PBVC/y reduced treated 3.5 mg/kg (–0.56% 0.68, p = 0.010) and...
Background: In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study, Cladribine significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting sclerosis. Objective: Describe two clinically relevant definitions for high disease activity (HDA) at baseline of study (utility verified receiving assess treatment effects 3.5 mg/kg compared overall population. Methods: Outcomes randomised to or placebo were...
<h3>Objective</h3> To evaluate the safety and efficacy of cladribine tablets in patients still experiencing active relapsing MS despite interferon (IFN)-β treatment. <h3>Methods</h3> A 96-week phase II study, randomizing treated with IFN-β to 3.5 mg/kg/IFN-β or placebo/IFN-β. Patients were receive placebo/IFN-β a 2:1 ratio (n = 172) exploratory outcomes being assessed. <h3>Results</h3> Adverse events (AEs) serious AEs similar across treatment groups, except lymphopenia. Fifty 124 (40.3%)...
The CLARITY and Extension studies demonstrated that treatment of relapsing-remitting multiple sclerosis (RRMS) with cladribine tablets (CT) results in significant clinical improvements, compared placebo. This paper presents the key magnetic resonance imaging (MRI) findings from study.Patients who received a cumulative dose either CT 3.5 or 5.25 mg/kg were rerandomized to placebo Extension. Patients arm assigned mg/kg. MRI assessments carried out when patients entered after Weeks 24, 48, 72...
We report the familial occurrence and apparent autosomal dominant inheritance of alternating hemiplegia childhood. The proband, a 9-year-old boy, presented with developmental retardation, rare tonic-clonic seizures, frequent episodes flaccid that had been presumed to represent postictal paralysis. spells, which started in his first year, did not respond multiple antiepileptics. Between attacks, there was choreoathetosis dystonic posturing. Father, brother, paternal uncle, grandmother similar...
Although protein receptors on the plasma membrane involved in initial steps of productive HIV-1 infection have been well characterized, little is known about interactions between cellular carbohydrate and HIV-1. Here, we report involvement a receptor, macrophage mannose receptor (MR), its role supporting binding entry. can enter cytoplasm human macrophages microglia as murine by MR, although no subsequent viral replication was observed. Correspondingly, entry into Cos-7 cells after induction...
Although use of contraception was pre-specified during cladribine clinical trials for multiple sclerosis, some pregnancies did occur. This analysis reports on pregnancy outcomes in the development program. Pregnancy female patients (direct pregnancies) and those arising from partner (i.e., partners male study participants with sclerosis) were evaluated an integrated safety ten studies sclerosis (nine a long-term registry), treated tablets, parenteral cladribine, or placebo (all-exposed...