A5042618140- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Parkinson's Disease Mechanisms and Treatments
- Retinal Development and Disorders
- Genetic Neurodegenerative Diseases
- Neurological diseases and metabolism
- Genetics and Neurodevelopmental Disorders
- Alzheimer's disease research and treatments
- Genomics and Rare Diseases
- Circadian rhythm and melatonin
- Connexins and lens biology
- Retinal and Optic Conditions
- Voice and Speech Disorders
- RNA modifications and cancer
- Dysphagia Assessment and Management
- RNA Research and Splicing
- Glaucoma and retinal disorders
- Autophagy in Disease and Therapy
- Prion Diseases and Protein Misfolding
- Light effects on plants
- Heme Oxygenase-1 and Carbon Monoxide
- Olfactory and Sensory Function Studies
- Older Adults Driving Studies
- Management of metastatic bone disease
- Lysosomal Storage Disorders Research
University of Pennsylvania
2010-2025
Children's Hospital of Philadelphia
2022-2024
Edwards Comprehensive Cancer Center
2024
Philadelphia University
2023-2024
Hospital of the University of Pennsylvania
2015
Penn Presbyterian Medical Center
2010-2013
Pennsylvania State University
2012
After successful gene therapy to correct retinal degeneration in one eye, treatment of the second eye is safe and effective—even when immunity vector present—in nonhuman primates dogs.
Genetic testing is now the standard of care for many neurologic conditions. Health disparities are unfortunately widespread in US health system, but utilization genetic conditions have not been studied. We tested hypothesis that access to and results vary according race, ethnicity, sex, socioeconomic status, insurance status adults with
Abstract Alternative splicing of neuronal genes is controlled partly by the coordinated action polypyrimidine tract binding proteins (PTBPs). While PTBP1 ubiquitously expressed, PTBP2 predominantly neuronal. Here, we define footprint in human transcriptome using brain tissue and induced pluripotent stem cell-derived neurons (iPSC-neurons). We map sites, characterize PTBP2-dependent alternative events, identify novel targets including SYNGAP1 , a synaptic gene whose loss-of-function leads to...
Background Parkinson's disease (PD) is a progressive neurodegenerative affecting about 5 million people worldwide with no disease-modifying therapies. We sought blood-based biomarkers in order to provide molecular characterization of individuals PD for diagnostic confirmation and prediction progression. Methods findings In 141 plasma samples (96 PD, 45 neurologically normal control [NC] individuals; 45.4% female, mean age 70.0 years) from longitudinally followed Discovery Cohort based at the...
Adeno-associated virus-mediated gene replacement is emerging as a safe and effective means of correcting single-gene mutations affecting the CNS. AAV-mediated progranulin (GRN) delivery has been proposed treatment for GRN-deficient frontotemporal dementia neuronal ceroid lipofuscinosis, recent studies using intraparenchymal AAV-Grn to brain have shown moderate success in histopathologic behavioral rescue mouse models. Here, we used AAV9 deliver GRN lateral ventricle achieve widespread...
Objective Plasma phosphorylated tau (p‐tau 181 ) is reliably elevated in Alzheimer's disease (AD), but less explored its specificity relative to other neurodegenerative conditions. Here, we find novel evidence that plasma p‐tau amyotrophic lateral sclerosis (ALS), a condition typically lacking pathology. We performed detailed evaluation identify the clinical correlates of ALS. Methods Patients were clinically or pathologically diagnosed with ALS (n = 130) AD 79), healthy non‐impaired...
Objective Amyotrophic Lateral Sclerosis (ALS) is a heterogeneous neurodegenerative condition featuring variable degrees of motor and cognitive impairment. We assessed the impact specific, empirically derived occupational skills requirements on functioning in ALS.
Biallelic loss-of-function mutations in the sorbitol dehydrogenase (SORD) gene cause most common recessive type of Charcot-Marie-Tooth disease (CMT), CMT-SORD. However, full genotype-phenotype spectrum and progression remain to be defined. Notably, a multicenter phase 2/3 study test efficacy govorestat (NCT05397665), new aldose reductase inhibitor, is currently ongoing. Diagnosing CMT-SORD will become imperative when disease-modifying therapies available. In this cross-sectional multicentre...
Cell death can be induced by exogenous reactive oxygen species (ROS). Endogenous ROS also play a role in cell triggered agents that are not themselves ROS. One of the most potent ROS-generating systems is iron-catalyzed Fenton reaction. Herein, authors tested whether iron plays an important diverse stimuli retinal pigment epithelial (RPE) cells.The ability chelator salicylaldehyde isonicotinoyl hydrazone (SIH) to chelate intracellular labile was human line ARPE-19. The SIH protect against...
SLOB binds to and modulates the activity of Drosophila Slowpoke (dSlo) calcium activated potassium channel. Recent microarray analyses demonstrated circadian cycling slob mRNA. We report mRNA protein expression pattern in heads. transcript is present photoreceptors, optic lobe, pars intercerebralis (PI) neurons surrounding brain cortex. exhibits a similar distribution pattern, we show that it cycles heads, photoreceptor cells neurosecretory PI. The altered various clock gene mutants,...
Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron death due to nuclear loss and cytoplasmic aggregation of the splice factor TDP-43. Pathologic TDP-43 associates with stress granules (SGs) downregulating SG-associated protein Ataxin-2 (Atxn2) using antisense oligonucleotides (ASO) prolongs survival in TAR4/4 sporadic ALS mouse model, a strategy now clinical trials. Here, we used AAV-mediated RNAi delivery achieve lasting targeted Atxn2 knockdown after single injection. To...
Abstract Background TDP-43 proteinopathies represent a spectrum of neurological disorders, anchored clinically on either end by amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The ALS–FTD exhibits diverse range clinical presentations with overlapping phenotypes, highlighting its heterogeneity. This study was aimed to use disease progression modeling identify novel data-driven spatial temporal subtypes brain atrophy in the spectrum. Methods We used procedure 13...
Advances in gene-specific therapeutics for patients with neuromuscular disorders (NMDs) have brought increased attention to the importance of genetic diagnosis. Genetic testing practices vary among adult clinics, multi-gene panel currently being most common approach; follow-up using broad-based methods, such as exome or genome sequencing, is less consistently offered. Here, we use five case examples illustrate unique ability improve diagnostic yield, resulting identification SORD-neuropathy,...
Advances in gene-specific therapeutics for patients with neuromuscular disorders (NMDs) have brought increased attention to the importance of genetic diagnosis. Genetic testing practices vary among adult clinics, multi-gene panel currently being most common approach; follow-up using broad-based methods, such as exome or genome sequencing, is less consistently offered. Here, we use five case examples illustrate unique ability improve diagnostic yield, resulting identification
Amyotrophic Lateral Sclerosis (ALS) is a heterogeneous neurodegenerative condition featuring variable degrees of motor decline and cognitive impairment. We test the hypothesis that reserve (CR), defined by occupational histories involving more complex demands, may protect against decline, while (MR), working jobs requiring skills, dysfunction.
Abstract Introduction/Aims The aim of this study was to examine clinical utilization and discontinuation rates sodium phenylbutyrate‐taurursodiol (PB‐TURSO) in a single Amyotrophic Lateral Sclerosis (ALS) center. PB‐TURSO approved by the United States Food Drug Administration (FDA) September 2022. Prior experience has been limited trials or expanded access protocols. In manuscript, we discuss insurance approval rates, patient uptake, large academic Methods Records patients seen for visits...
Pupillometry is used clinically to evaluate retinal and optic nerve health by measuring pupillary function in response light stimuli. We have developed an algorithm using murine pupillometric measurements automate the analysis of data. The raw data filtered thresholding remove caused eye blinking, loss pupil tracking, and/or head movement. Twelve physiologically relevant parameters are extracted from collected Algorithm derived values do not deviate significantly manually calculated (p ¿...
In behavioral-variant frontotemporal degeneration (bvFTD) and amyotrophic lateral sclerosis (ALS), secondary motor or cognitive-behavioral symptoms, respectively, are associated with shorter survival. However, factors influencing symptom development remain largely unexplored. We performed a retrospective evaluation of the entire disease course individuals ALS (n=172) bvFTD (n=69). Only who had neuropathological confirmation TDP-43 proteinopathy at autopsy
Abstract Background Comorbid cognitive impairment in amyotrophic lateral sclerosis (i.e., ALS‐FTD), is associated with adverse clinical outcomes and survival. It often exhibits features of behavioral variant frontotemporal dementia (bvFTD) and/or non‐fluent agrammatic primary progressive aphasia (naPPA). Traditional assessments, such as the Edinburgh Cognitive Assessment Scale (ECAS), require trained personnel for administration. An additional repeatable, objective approach involves...
Abstract Background In amyotrophic lateral sclerosis and behavioral‐variant frontotemporal degeneration, the presence of secondary cognitive‐behavioral or motor symptoms, respectively, is associated with shorter survival. However, factors influencing risk symptom development remain largely unexplored time‐to‐event characterization for developing symptoms important prognostic clinical decision‐making. Method We performed a retrospective evaluation entire disease course individuals in Penn...