A5032465628- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Nerve injury and regeneration
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neuropharmacology Research
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- Autism Spectrum Disorder Research
- Nuclear Receptors and Signaling
- Neuroscience and Neural Engineering
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetic Neurodegenerative Diseases
- Advanced MRI Techniques and Applications
- Botulinum Toxin and Related Neurological Disorders
- Peroxisome Proliferator-Activated Receptors
- Advanced biosensing and bioanalysis techniques
- RNA regulation and disease
- Stress Responses and Cortisol
- Cerebral Palsy and Movement Disorders
- Advanced Neuroimaging Techniques and Applications
- Glioma Diagnosis and Treatment
- Biomedical Ethics and Regulation
- Tryptophan and brain disorders
University of Wisconsin–Madison
2016-2025
Centre for Biomedical Engineering and Physics
2014-2024
University of Wisconsin System
2011-2022
McGill University
2009
Rush University
2000-2006
University of Illinois Urbana-Champaign
2006
University of Illinois Chicago
2002-2006
Rush University Medical Center
1999-2003
Presbyterian St. Luke's Medical Center
1999-2003
Texas Health Dallas
2000-2002
Lentiviral delivery of glial cell line–derived neurotrophic factor (lenti-GDNF) was tested for its trophic effects upon degenerating nigrostriatal neurons in nonhuman primate models Parkinson's disease (PD). We injected lenti-GDNF into the striatum and substantia nigra nonlesioned aged rhesus monkeys or young adult treated 1 week prior with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Extensive GDNF expression anterograde retrograde transport seen all animals. In monkeys, augmented...
The primate striatum contains tyrosine hydroxylase (TH)-immunoreactive (ir) neurons, the numbers of which are augmented after dopamine depletion. Glial cell line-derived neurotrophic factor (GDNF) strongly modulates viability and phenotypic expression ventral mesencephalic neurons. effect GDNF on TH-ir neurons intrinsic to has yet be investigated. In present study, stereological counts striatal in aged parkinsonian nonhuman primates revealed that delivered via a lentiviral vector (lenti-)...
By sequentially applying sonic hedgehog (C25II) and CHIR99021 (GSK3β inhibitor) to induce the midbrain floor plate (FP) progenitors fibroblast growth factor 8 (FGF8) promote dopaminergic differentiation in a chemically defined medium, we have established robust system for generation of dopamine (DA) neurons from human rhesus monkey embryonic stem cells induced pluripotent (PSCs). We found that specifies diencephalon hind brain fates concentration-dependent manner only narrow concentration...
Activation of the peroxisome proliferator-activated receptor gamma (PPAR-γ) has been proposed as a possible neuroprotective strategy to slow down progression early Parkinson's disease (PD). Here we report preclinical data on use PPAR-γ agonist pioglitazone (Actos®; Takeda Pharmaceuticals Ltd.) in paradigm resembling PD nonhuman primates.Rhesus monkeys that were trained perform battery behavioral tests received single intracarotid arterial injection 20 ml saline containing 3 mg dopaminergic...
The generation of induced pluripotent stem cells (iPSCs) opens up the possibility for personalized cell therapy. Here, we show that transplanted autologous rhesus monkey iPSC-derived neural progenitors survive to 6 months and differentiate into neurons, astrocytes, myelinating oligodendrocytes in brains MPTP-induced hemiparkinsonian monkeys with a minimal presence inflammatory reactive glia. This finding represents significant step toward regenerative therapies.
Parkinson's disease (PD) is associated with increased excitatory activity within the subthalamic nucleus (STN). We sought to inhibit STN output in hemiparkinsonian macaques by transfection adeno-associated virus (AAV) containing gene for glutamic acid decarboxylase (GAD). In total, 13 were rendered right intracarotid 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine injection. Seven animals injected AAV-GAD into STN, and six received an AAV green fluorescent protein (GFP). Videotaped motor...
Human neural progenitor cells (hNPCs) have been proposed as a potential source of for ex vivo gene therapy. In this pilot study, three 5-year-old female cynomolgus monkeys received single intracarotid infusion MPTP, followed 1 week later by MRI-guided stereotaxic intrastriatal and intranigral injections male hNPCs transgenic GDNF. Immunosupression with oral cyclosporine (30–40 mg/kg) began 48 h before hNPC transplants continued throughout the study. We monitored animals using clinical rating...
Review of first-in-human trials should safeguard the integrity scientific enterprise through a focus on preclinical and clinical study quality.
Glial cell line derived neurotrophic factor (GDNF) is a that has neuroprotective effects in animal models of Parkinson's disease (PD) and been proposed as PD therapy. GDNF does not cross the blood brain barrier (BBB), requires direct intracerebral delivery to be effective. Trojan horse technology, which coupled monoclonal antibody (mAb) against human insulin receptor (HIR), allow BBB transport (ArmaGen Technologies Inc.). In this study we tested feasibility HIRMAb-GDNF induce neuroprotection...
Abstract Leucine-rich repeat kinase 2 (LRRK2) G2019S is a relatively common mutation, associated with 1–3% of Parkinson’s disease (PD) cases worldwide. hypothesized to increase LRRK2 activity. Dopaminergic neurons derived from induced pluripotent stem cells PD patients carrying are reported have several phenotypes compared wild type controls, including increased activated caspase-3 and reactive oxygen species (ROS), autophagy dysfunction, simplification neurites. The marmoset envisioned as...
Alzheimer's (AD), Huntington's (HD), and Parkinson's (PD) disease are age-related neurodegenerative disorders characterized by progressive neuronal cell death. Although each has particular pathologies symptoms, accumulated evidence points to similar mechanisms of neurodegeneration, including inflammation, oxidative stress, protein aggregation. A significant body research is ongoing understand how these pathways affect other what ultimately triggers the onset disease. Experiments in nonhuman...