A5071390726- Amyotrophic Lateral Sclerosis Research
- Autoimmune Neurological Disorders and Treatments
- Peripheral Neuropathies and Disorders
- Neurogenetic and Muscular Disorders Research
- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- Inflammatory Myopathies and Dermatomyositis
- Endoplasmic Reticulum Stress and Disease
- Genetic Neurodegenerative Diseases
- Hereditary Neurological Disorders
- Peripheral Nerve Disorders
- Mitochondrial Function and Pathology
- Parkinson's Disease Mechanisms and Treatments
- Nerve Injury and Rehabilitation
- Eosinophilic Disorders and Syndromes
- Parkinson's Disease and Spinal Disorders
- Genetics and Neurodevelopmental Disorders
- Neurofibromatosis and Schwannoma Cases
- Muscle Physiology and Disorders
- Adenosine and Purinergic Signaling
- Infectious Encephalopathies and Encephalitis
- Intracerebral and Subarachnoid Hemorrhage Research
- Alzheimer's disease research and treatments
- History of Medical Practice
- Orthopedic Surgery and Rehabilitation
Washington University in St. Louis
2016-2025
Harvard University
2022
Biogen (United States)
2022
Massachusetts General Hospital
2022
Barnes-Jewish Hospital
2012-2022
Mallinckrodt (United States)
2018-2022
James S. McDonnell Foundation
2022
University Hospital Magdeburg
2021
Jewish Hospital
2021
Mayo Clinic in Florida
2021
The intrathecally administered antisense oligonucleotide tofersen reduces synthesis of the superoxide dismutase 1 (SOD1) protein and is being studied in patients with amyotrophic lateral sclerosis (ALS) associated mutations SOD1 (SOD1 ALS).
Tofersen is an antisense oligonucleotide that mediates the degradation of superoxide dismutase 1 (SOD1) messenger RNA to reduce SOD1 protein synthesis. Intrathecal administration tofersen being studied for treatment amyotrophic lateral sclerosis (ALS) due mutations.We conducted a phase 1-2 ascending-dose trial evaluating in adults with ALS mutations. In each dose cohort (20, 40, 60, or 100 mg), participants were randomly assigned 3:1 ratio receive five doses placebo, administered...
Despite extensive research, amyotrophic lateral sclerosis (ALS) remains a progressive and invariably fatal neurodegenerative disease. Limited knowledge of the underlying causes ALS has made it difficult to target upstream biological mechanisms disease, therapeutic interventions are usually administered relatively late in course Genetic forms offer unique opportunity for development, as genetic associations may reveal potential insights into disease etiology. also be amenable investigating...
Abstract Objective Patients with amyotrophic lateral sclerosis (ALS) caused by superoxide dismutase 1 (SOD1) gene mutations (SOD1 ALS) treated tofersen have shown slowing of disease progression, and stabilization recovery function in some patients. We report our clinical experience treating patients SOD1 ALS the effects on outcome measures. Methods This was a single‐center observational study receiving treatment tofersen. The neurofilament levels, muscle strength, measures were assessed....
To analyze clinical features and myopathology changes in muscle fibers, connective tissue, vessels 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody-associated myopathies.Retrospective review of records myopathologic 49 consecutive patients with myopathies serum HMGCR antibodies.Clinical included onset age from 12 to 83 years, female predominance (67%), proximal, symmetric weakness (84%), discomfort (78%), dysphagia (35%), systemic features, including skin rash interstitial...
Multisystem proteinopathy (MSP) involves disturbances of stress granule (SG) dynamics and autophagic protein degradation that underlie the pathogenesis a spectrum degenerative diseases affect muscle, brain, bone. Specifically, identical mutations in adaptor SQSTM1 can cause varied penetrance 4 distinct phenotypes: amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Paget's disease bone, distal myopathy. It has been hypothesized clinical pleiotropy relates to additional genetic...
To identify and characterize myeloid cell populations within the CSF of patients with MS anti-myelin oligodendrocyte glycoprotein (MOG) disorder by high-resolution single-cell gene expression analysis.Single-cell RNA sequencing (scRNA-seq) was used to profile individual cells blood from 2 subjects relapsing-remitting (RRMS) one anti-MOG disorder. Publicly available scRNA-seq data HIV were also analyzed. An informatics pipeline cluster transcriptomic profiling. Based on cells, a flow...
<h3>Objective:</h3> To identify the genetic etiology and characterize clinicopathologic features of a novel distal myopathy. <h3>Methods:</h3> We performed whole-exome sequencing on family with an autosomal dominant myopathy targeted exome in 1 patient sporadic myopathy, both rimmed vacuolar pathology. also evaluated pathogenicity identified mutations using immunohistochemistry, Western blot analysis, expression studies. <h3>Results:</h3> Sequencing likely pathogenic c.1165+1 G>A splice...
To determine whether neuronal and neuroaxonal injury, neuroinflammation, synaptic dysfunction associate with clinical course outcomes in antibody-mediated encephalitis (AME), we measured biomarkers of these processes CSF from patients presenting AME cognitively normal individuals.Biomarkers (total tau, VILIP-1) damage (neurofilament light chain [NfL]), inflammation (YKL-40), function (neurogranin, SNAP-25) were obtained 45 at the time diagnosis NMDA receptor (n = 34) or LGI1/CASPR2 11) 39...
Therapeutic strategies that target disease-associated transcripts are being developed for a variety of neurodegenerative syndromes. Protein levels change as function their half-life, property critically influences the timing and application therapeutics. In addition, both protein kinetics concentration may play important roles in neurodegeneration; therefore, it is essential to understand vivo kinetics, including half-life. Here, we applied stable isotope-labeling technique combination with...
BACKGROUNDWolfram syndrome is a rare ER disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration. Although there no treatment for Wolfram syndrome, preclinical studies in cell rodent models suggest that therapeutic strategies targeting calcium homeostasis, including dantrolene sodium, may be beneficial.METHODSBased on results from sodium ongoing longitudinal studies, we assembled what believe the first-ever clinical trial pediatric...
We sought to determine clinical significance of neuronal septin autoimmunity and evaluate for potential IgG effects.Septin-IgGs were detected by indirect immunofluorescence assays (IFAs; mouse tissue cell based) or Western blot. binding (and internalization of) extracellular epitopes evaluated live rat hippocampal neuron assay. The impact purified patient IgGs on murine cortical function was determined recording field potentials in a multielectrode array platform.Septin-IgGs identified 23...
Accumulation of misfolded superoxide dismutase-1 (SOD1) is a pathological hallmark SOD1-related amyotrophic lateral sclerosis (ALS) and observed in sporadic ALS where its role pathogenesis controversial. Understanding vivo protein kinetics may clarify how SOD1 influences neurodegeneration inform optimal dosing for therapies that lower transcripts.We employed stable isotope labeling paired with mass spectrometry to evaluate concentration soluble cerebrospinal fluid (CSF) mutation carriers,...
ABSTRACT Introduction/Aims Tofersen is approved for the treatment of amyotrophic lateral sclerosis (ALS) due to superoxide dismutase 1 mutations ( SOD1 ‐ALS). Here we report serious neurologic adverse events (AEs) that occurred in tofersen clinical trials people with ‐ALS. Methods Serious AEs myelitis, radiculitis, aseptic meningitis, and papilledema reported are described. were defined according International Conference Harmonization guidelines, diagnosed by investigators based on symptoms,...
Associations between sleep and neurodegenerative diseases have become increasingly evident. This study aims to characterize the prevalence type of pathology in Creutzfeldt-Jakob disease (CJD), a rapidly progressive, fatal disease.In this observational cross-sectional cohort study, we performed retrospective analysis signs symptoms consecutive group patients with definite CJD at tertiary care medical center (n = 28). Polysomnography was 14 patients.Although only 5 28 carried premorbid...