A5031853409- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Parkinson's Disease Mechanisms and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Pluripotent Stem Cells Research
- Nerve injury and regeneration
- biodegradable polymer synthesis and properties
- Prion Diseases and Protein Misfolding
- Neuroscience and Neural Engineering
- Spinal Cord Injury Research
- Neuroscience and Neuropharmacology Research
- EEG and Brain-Computer Interfaces
- Neurological diseases and metabolism
- Genetic Neurodegenerative Diseases
- Alzheimer's disease research and treatments
- Conducting polymers and applications
- Muscle activation and electromyography studies
- GABA and Rice Research
- Neural dynamics and brain function
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Epigenetics and DNA Methylation
- Cholinesterase and Neurodegenerative Diseases
- Neurological disorders and treatments
Johns Hopkins University
2016-2025
Johns Hopkins Medicine
2015-2024
Johns Hopkins Hospital
2010-2024
Cedars-Sinai Medical Center
2024
University Medical Center Utrecht
2023
Johns Hopkins University Applied Physics Laboratory
2023
Xenon Pharmaceuticals (Canada)
2021
University of California, San Diego
2011
SUNY Upstate Medical University
2011
University of Miami
2011
Transgenic overexpression of Cu +2 /Zn superoxide dismutase 1 (SOD1) harboring an amyotrophic lateral sclerosis (ALS)-linked familial genetic mutation ( SOD1 G93A ) in a Sprague–Dawley rat results ALS-like motor neuron disease. Motor disease these rats depended on high levels mutant expression, increasing from 8-fold over endogenous the spinal cord young presymptomatic to 16-fold end-stage animals. Disease onset was early, ≈115 days, and progression very rapid thereafter with affected...
Reactive astrocytes are thought to protect the penumbra during brain ischemia, but direct evidence has been lacking due absence of suitable experimental models. Previously, we generated mice deficient in two intermediate filament (IF) proteins, glial fibrillary acidic protein (GFAP) and vimentin, whose upregulation is hallmark reactive astrocytes. GFAP −/− Vim exhibit attenuated posttraumatic gliosis, improved integration neural grafts, regeneration. Seven days after middle cerebral artery...
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...
Answer ALS is a biological and clinical resource of patient-derived, induced pluripotent stem (iPS) cell lines, multi-omic data derived from iPS neurons longitudinal smartphone over 1,000 patients with ALS. This provides population-level that may be employed to identify clinical-molecular-biochemical subtypes amyotrophic lateral sclerosis (ALS). A unique smartphone-based system was collect deep data, including fine motor activity, speech, breathing linguistics/cognition. The spinal were...
Abstract Objective We explored the potential of embryonic stem cell–derived motor neurons to functionally replace those cells destroyed in paralyzed adult rats. Methods administered a phosphodiesterase type 4 inhibitor and dibutyryl cyclic adenosine monophosphate overcome myelin‐mediated repulsion provided glial neurotrophic factor within sciatic nerve attract transplanted axons toward skeletal muscle targets. Results found that these strategies significantly increased success extending out...
Recent studies highlight astrocytes as key drivers of motor neuron (MN) degeneration and disease propagation in mutant human superoxide dismutase 1 (mSOD1)-mediated amyotrophic lateral sclerosis. However, vivo analysis specific astrocytic influence sclerosis has proven difficult because mSOD1 is ubiquitously expressed throughout the CNS rodent models studied. Here, we transplanted SOD1 G93A glial-restricted precursor cells—glial progenitors capable differentiating into astrocytes—into...
Amyotrophic lateral sclerosis (ALS), a fatal and progressive neurodegenerative disorder characterized by weakness, muscle atrophy, spasticity, is the most common adult-onset motor neuron disease. Although majority of ALS cases are sporadic, ∼5–10% familial, including those linked to mutations in SOD1 (Cu/Zn superoxide dismutase). Missense dynactin gene ( DCTN1 ) encoding p150 Glued subunit have been both familial sporadic ALS. To determine molecular mechanism whereby mutant causes selective...
Duchenne muscular dystrophy (DMD) remains an intractable genetic disease. Althogh there are several animal models of DMD, is no human cell model that carries patient-specific DYSTROPHIN mutations. Here, we present a DMD using induced pluripotent stem cells (hiPSCs). Our reveals concordant disease-related phenotypes with patient-dependent variation, which partially reversed by and pharmacological approaches. "chemical-compound-based" strategy successfully directs hiPSCs into expandable...
Electrical impedance myography (EIM), a non-invasive, electrophysiological technique, has preliminarily shown value as an ALS biomarker. Here we perform multicenter study to further assess EIM’s potential for tracking ALS. patients were enrolled across eight sites. Each subject underwent EIM, handheld dynamometry (HHD), and the Functional Rating Scale-revised (ALSFRS-R) regularly. Techniques compared by assessing coefficient of variation (CoV) in rate decline each technique’s correlation...
Improved outcome measures are necessary to reduce sample size and increase power in amyotrophic lateral sclerosis (ALS) clinical trials. Motor unit number estimation (MUNE) is a potentially attractive tool. MUNE methods previously employed multicenter trials exhibited excessive variability were prone artifact.To evaluate modification of standard incremental natural history study subjects with ALS.Fifty healthy evaluated twice 71 ALS studied repeatedly for up 500 days. Side nerve was based on...
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons in the CNS. Astrocytes play critical role progression ALS. are interconnected through family gap junction proteins known as connexins (Cx). Cx43 major astrocyte connexin conducting crucial homeostatic functions Under pathological conditions, expression and altered. Here we report that an abnormal increase serves one mechanisms for astrocyte‐mediated toxicity We observed SOD1...
Astrocytes from familial amyotrophic lateral sclerosis (ALS) patients or transgenic mice are toxic specifically to motor neurons (MNs). It is not known if astrocytes sporadic ALS (sALS) cause MN degeneration in vivo and whether the effect specific MNs. By transplanting spinal neural progenitors, derived sALS healthy induced pluripotent stem cells (iPSCs), into cervical cord of adult SCID for 9 months, we found that differentiated human were present large areas cord, replaced endogenous...
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of the motor nervous system. Clinical studies have demonstrated cortical and spinal neuron hyperexcitability using transcranial magnetic stimulation threshold tracking nerve conduction studies, respectively, although metrics excitability not been used as pharmacodynamic biomarkers in multi-site clinical trials.To ascertain whether ezogabine decreases ALS.This double-blind, placebo-controlled phase 2 randomized...
Connexin 43 (Cx43) gap junctions and hemichannels mediate astrocyte intercellular communication in the central nervous system under normal conditions contribute to astrocyte-mediated neurotoxicity amyotrophic lateral sclerosis (ALS). Here, we show that astrocyte-specific knockout of Cx43 a mouse model ALS slows disease progression both spatially temporally, provides motor neuron (MN) protection, improves survival. In addition, expression is up-regulated human postmortem tissue cerebrospinal...
Abstract Brain‐computer interfaces (BCIs) can be used to control assistive devices by patients with neurological disorders like amyotrophic lateral sclerosis (ALS) that limit speech and movement. For control, it is desirable for BCI systems accurate reliable, preferably minimal setup time. In this study, a participant severe dysarthria due ALS operates computer applications six intuitive commands via chronic electrocorticographic (ECoG) implant over the ventral sensorimotor cortex. Speech...