A5011997502- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Neurotransmitter Receptor Influence on Behavior
- Neuroscience and Neuropharmacology Research
- Amyotrophic Lateral Sclerosis Research
- Computational Drug Discovery Methods
- Dementia and Cognitive Impairment Research
- Neurological disorders and treatments
- Neurogenetic and Muscular Disorders Research
- Botulinum Toxin and Related Neurological Disorders
- S100 Proteins and Annexins
- Cholinesterase and Neurodegenerative Diseases
- Epigenetics and DNA Methylation
- 14-3-3 protein interactions
- Nerve injury and regeneration
- Receptor Mechanisms and Signaling
- Stress Responses and Cortisol
- Neuroendocrine regulation and behavior
- Nuclear Receptors and Signaling
- Coccidia and coccidiosis research
- Animal Nutrition and Physiology
- Cell Image Analysis Techniques
- Glycosylation and Glycoproteins Research
- Pharmacological Effects and Assays
- Lysosomal Storage Disorders Research
Biogen (United States)
2017-2025
United States Department of Agriculture
2021-2025
University of Arkansas System
2023-2025
Joint Genome Institute
2024-2025
Lawrence Berkeley National Laboratory
2024-2025
Western University
2023-2024
Biogen (United Kingdom)
2024
University of Nebraska–Lincoln
2017-2023
University of Tennessee at Knoxville
2023
Novant Health
2023
Mice experiencing repeated aggression develop a long-lasting aversion to social contact, which can be normalized by chronic, but not acute, administration of antidepressant. Using viral-mediated, mesolimbic dopamine pathway-specific knockdown brain-derived neurotrophic factor (BDNF), we showed that BDNF is required for the development this experience-dependent aversion. Gene profiling in nucleus accumbens indicates local obliterates most effects on gene expression within circuit, with...
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...
Aggregated α-synuclein plays an important role in Parkinson's disease pathogenesis. Cinpanemab, a human-derived monoclonal antibody that binds to α-synuclein, is being evaluated as disease-modifying treatment for disease.In 52-week, multicenter, double-blind, phase 2 trial, we randomly assigned, 2:1:2:2 ratio, participants with early receive intravenous infusions of placebo (control) or cinpanemab at dose 250 mg, 1250 3500 mg every 4 weeks, followed by active-treatment dose-blinded extension...
Mutations in superoxide dismutase 1 (SOD1) are responsible for 20% of familial ALS. Given the gain toxic function this dominantly inherited disease, lowering SOD1 mRNA and protein is predicted to provide therapeutic benefit. An early generation antisense oligonucleotide (ASO) targeting was identified tested a phase I human clinical trial, based on modest protection animal models Although trial provided encouraging safety data, drug not advanced because there progress designing other, more...
Abstract Background Pathological and genetic evidence implicates toxic effects of aggregated α‐synuclein in the pathophysiology neuronal dysfunction degeneration Parkinson's disease. Immunotherapy targeting is a promising strategy for delaying disease progression. Objective This study (NCT02459886) evaluated safety, tolerability, pharmacokinetics BIIB054, human‐derived monoclonal antibody that preferentially binds to α‐synuclein, healthy volunteers participants with Methods A total 48 (age...
Tau plays a key role in Alzheimer's disease (AD) pathophysiology, and accumulating evidence suggests that lowering tau may reduce this pathology. We sought to inhibit MAPT expression with tau-targeting antisense oligonucleotide (MAPT
Abstract Background The objective of this study was to assess neurofilament light chain as a Parkinson's disease biomarker. Methods We quantified in 2 independent cohorts: (1) longitudinal cerebrospinal fluid samples from the de novo cohort and (2) large with serum disease, other cognate/neurodegenerative disorders, healthy controls, prodromal conditions, mutation carriers. Results In Progression Marker Initiative cohort, mean baseline higher patients (13 ± 7.2 pg/mL) than controls (12 6.7...
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...
Leucine-rich repeat kinase 2 (LRRK2) inhibition is a promising therapeutic approach for the treatment of Parkinson's disease (PD).The aim this study was to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics potent, selective, CNS-penetrant LRRK2 inhibitor BIIB122 (DNL151) in healthy participants patients with PD.Two randomized, double-blind, placebo-controlled studies were completed. The phase 1 (DNLI-C-0001) evaluated single multiple doses up 28 days participants. 1b...
The transcription factor deltaFosB (DeltaFosB), induced in nucleus accumbens (NAc) by chronic exposure to drugs of abuse, has been shown mediate sensitized responses these drugs. However, less is known about a role for DeltaFosB regulating natural rewards. Here, we demonstrate that two powerful reward behaviors, sucrose drinking and sexual behavior, increase levels the NAc. We then use viral-mediated gene transfer study how such induction influences behavioral overexpression NAc increases...
Chronic exposure to addictive drugs enhances cAMP response element binding protein (CREB)-regulated gene expression in nucleus accumbens (NAc), and these effects are thought reduce the positive hedonic of passive cocaine administration. Here, we used viral-mediated transfer produce short- long-term regulation CREB activity NAc shell rats engaging volitional self-administration. Increasing markedly enhanced reinforcement self-administration behavior, as indicated by leftward (long-term)...
Parkinson's disease (PD) is a prevalent neurodegenerative with no approved disease-modifying therapies. Multiplications, mutations, and single nucleotide polymorphisms in the SNCA gene, encoding α-synuclein (aSyn) protein, either cause or increase risk for PD. Intracellular accumulations of aSyn are pathological hallmarks Taken together, reduction production may provide therapy We show that antisense oligonucleotides (ASOs) reduce rodent preformed fibril (PFF) models Reduced leads to...
Four less well-studied but promising "emerging" cerebrospinal fluid (CSF) biomarkers are elevated in late-onset Alzheimer disease (AD): neurogranin, synaptosomal-associated protein-25 (SNAP-25), visinin-like protein 1 (VILIP-1), and chitinase-3-like (YKL-40).CSF SNAP-25, VILIP-1, YKL-40 were measured families carrying autosomal-dominant AD mutations.The four emerging CSF significantly the mutation carriers (n = 235) versus noncarriers 145). altered very early time course, approximately 15-19...
We tested the hypothesis that plasma neurofilament light chain (NfL) identifies asymptomatic carriers of familial frontotemporal lobar degeneration (FTLD)-causing mutations at risk disease progression.Baseline NfL concentrations were measured with single-molecule array in original (n = 277) and validation 297) cohorts. C9orf72, GRN, MAPT mutation noncarriers from same families classified by severity (asymptomatic, prodromal, full phenotype) using CDR Dementia Staging Instrument plus behavior...
Abstract Background There is currently a lack of reliable and easily accessible biomarkers predicting cognitive decline in Alzheimer’s disease (AD). Synaptic dysfunction loss occur early AD synaptic measured the brain tissue by PET are closely linked to decline, rendering proteins promising target for biomarker development. Methods We used novel Simoa assays measure cerebrospinal fluid (CSF) levels two candidates, postsynaptic density protein 95 (PSD-95/DLG4), presynaptically localized...