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Treatment of Parkinson's disease with biologics that penetrate the blood-brain barrier via receptor-mediated transport

FRONTIERS IN AGING NEUROSCIENCE (2023)

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Article Biochemistry & Molecular Biology

Peripheral Inflammatory Markers TNF-α and CCL2 Revisited: Association with Parkinson's Disease Severity

Georgia Xiromerisiou et al.

Summary: The study aimed to examine the levels of serum TNF-alpha and CCL2 in PD patients compared to healthy controls, and investigate their associations with clinical symptoms. The results showed that PD patients in advanced stages had higher levels of TNF-alpha in their serum, which was significantly associated with disease severity. However, no significant associations were found for CCL2 levels.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

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Review Biochemistry & Molecular Biology

Uncovering Novel Therapeutic Targets for Parkinson's Disease

Ritu Soni et al.

Summary: Parkinson's disease (PD) is a common progressive disorder characterized by deposition of inclusion bodies on dopaminergic neurons in the brain. The major component of these inclusion bodies is α-synuclein aggregates, which gradually propagate PD pathology. Underexplored molecular targets could potentially aid in the development of novel therapeutics for PD.

ACS CHEMICAL NEUROSCIENCE (2023)

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Article Pharmacology & Pharmacy

HCH6-1, an antagonist of formyl peptide receptor-1, exerts anti-neuroinflammatory and neuroprotective effects in cellular and animal models of Parkinson?s disease

Hung-Li Wang et al.

Summary: Microglial activation-induced neuroinflammation plays a role in the onset and progression of Parkinson's disease. Activated microglia secrete pro-inflammatory and neurotoxic cytokines, which contribute to neurodegeneration. This study suggests that the activation of microglia through FPR1 leads to loss of dopaminergic neurons by activating inflammasome and upregulating pro-inflammatory cytokines, and that the FPR1 antagonist HCH6-1 has a neuroprotective effect on dopaminergic neurons.

BIOCHEMICAL PHARMACOLOGY (2023)

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Review Biochemistry & Molecular Biology

Revisiting Alpha-Synuclein Pathways to Inflammation

Patricia Lyra et al.

Summary: The development of neurodegenerative disorders, such as Parkinson's Disease, is closely linked to inflammation and dysbiosis. Understanding the mechanistic pathways of alpha-synucleinopathies and the impact of microbial dysbiosis on alpha-Syn can provide insights into the management and prevention of these conditions, with a focus on inflammatory mitigation and microbial balance.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

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Review Neurosciences

Neuropathology of incidental Lewy body & prodromal Parkinson's disease

Thomas Koeglsperger et al.

Summary: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons. Previous studies have identified cellular and molecular changes that occur before the appearance of Lewy bodies (LBs) in these neurons. Understanding these early pathological events may help in the development of therapeutic and diagnostic strategies for PD.

MOLECULAR NEURODEGENERATION (2023)

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Review Clinical Neurology

Functional roles of reactive astrocytes in neuroinflammation and neurodegeneration

Rickie Patani et al.

Summary: Therapies that prevent neuronal loss in neuroinflammation and neurodegenerative disease are still elusive. This review highlights the importance of 'omics' technologies in characterizing the functional states of reactive astrocytes in different pathological scenarios.

NATURE REVIEWS NEUROLOGY (2023)

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Review Biochemistry & Molecular Biology

Brain gene therapy with Trojan horse lipid nanoparticles

William M. Pardridge

Summary: The COVID-19 mRNA vaccine uses scalable manufacturing of lipid nanoparticles (LNPs) to encapsulate mRNA. This large nucleic acid delivery technology has potential applications in gene therapy, including delivering plasmid DNA. To enable gene therapy for the brain, LNPs could be reformulated for brain delivery by attaching receptor-specific monoclonal antibodies (MAbs) to the LNP surface. The MAbs act as molecular Trojan horses, facilitating the transport of LNPs across the blood-brain barrier (BBB) and localization to the nucleus for therapeutic gene transcription.

TRENDS IN MOLECULAR MEDICINE (2023)

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Article Neurosciences

Parkinson's Disease Drug Therapies in the Clinical Trial Pipeline: 2023 Update

Kevin McFarthing et al.

Summary: Background: Annual reports have been generated since 2020 to review the clinical development of new drug-based therapies for Parkinson's disease (PD), focusing on symptomatic treatments (ST) and disease modifying treatments (DMT). A breakdown analysis of clinical trials obtained from ClinicalTrials.gov identified 139 active trials for PD drug therapies. Results: Of these trials, 55% were ST and 45% were DMT. A third were in Phase 1, half were in Phase 2, and 14% were in Phase 3. Novel therapies accounted for 42% of trials, with repurposed drugs in 35% of trials. Conclusions: The slow progress and lack of phase transitions are concerning, but efforts are being made to accelerate the clinical trial process for PD therapies.

JOURNAL OF PARKINSONS DISEASE (2023)

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Article Chemistry, Medicinal

Proof-of-Principle Study of Inflammasome Signaling Proteins as Diagnostic Biomarkers of the Inflammatory Response in Parkinson's Disease

Erika d. l. R. M. Cabrera Ranaldi et al.

Summary: Parkinson's disease is a neurodegenerative disorder characterized by the death of dopaminergic neurons, α-synuclein aggregates, and motor deficits. Inflammation is a major cause of dopaminergic neuronal loss. The inflammasome, a multiprotein complex, perpetuates neuroinflammation in Parkinson's disease and other neurodegenerative disorders.

PHARMACEUTICALS (2023)

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Review Biochemistry & Molecular Biology

Are Therapies That Target & alpha;-Synuclein Effective at Halting Parkinson's Disease Progression? A Systematic Review

Abbie T. Rodger et al.

Summary: Currently, there are no pharmacological treatments that can completely stop or reverse the progression of Parkinson's Disease (PD). Therefore, there is a need for neuroprotective therapies. This systematic review examines the effectiveness of anti-a-synuclein (a-syn) therapies in preventing PD progression in preclinical models and human clinical trials. The review found that novel preclinical anti-a-syn therapeutics reduced a-syn aggregations and protected against dopaminergic neuronal loss. Completed clinical trials showed significant tolerability and efficacy in reducing a-syn and minimal adverse effects. Overall, this review highlights the potential of anti-a-syn therapies in both preclinical and clinical settings to reduce a-syn accumulation and potentially slow down PD progression.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

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Article Multidisciplinary Sciences

Border-associated macrophages mediate the neuroinflammatory response in an alpha-synuclein model of Parkinson disease

A. M. Schonhoff et al.

Summary: Neuroinflammatory mechanisms are involved in Parkinson disease. We identified border-associated macrophages (BAMs) as crucial for the α-synuclein-mediated neuroinflammatory response through class II antigen presentation and T cell infiltration. Our findings highlight the role of BAMs in mediating the pathogenesis of Parkinson disease.

NATURE COMMUNICATIONS (2023)

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Editorial Material Clinical Neurology

Editorial: Biomarkers of non-motor symptoms in Parkinson's disease and parkinsonisms

Massimo Filippi et al.

FRONTIERS IN NEUROLOGY (2023)

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Review Biochemistry & Molecular Biology

Soluble forms of cytokine and growth factor receptors: mechanisms of generation and modes of action in the regulation of local and systemic inflammation

Eirini Kefaloyianni

Summary: Cytokine and growth factor receptors can exist in soluble forms and play important roles in cell signaling. They can compete for ligand binding, stabilize ligands, or activate additional signaling events. Soluble receptors also function in remote cells and organs.

FEBS LETTERS (2022)

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Article Chemistry, Medicinal

Kinetics of Blood-Brain Barrier Transport of Monoclonal Antibodies Targeting the Insulin Receptor and the Transferrin Receptor

William M. Pardridge

Summary: Biologic drugs are large molecule pharmaceuticals that cannot cross the blood-brain barrier. They can be re-engineered for BBB transport as IgG fusion proteins. The kinetics of BBB transport can be quantified with mathematical models.

PHARMACEUTICALS (2022)

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Review Pharmacology & Pharmacy

Blood-brain barrier delivery for lysosomal storage disorders with IgG-lysosomal enzyme fusion proteins

William M. Pardridge

Summary: The majority of lysosomal storage diseases affect the brain. The current intravenous enzyme replacement therapy is not effective because the recombinant lysosomal enzymes cannot cross the blood-brain barrier (BBB). However, by re-engineering biologic drugs into IgG-enzyme fusion proteins, it is possible to deliver the lysosomal enzymes to the brain through the BBB. This approach utilizes the IgG domain of the fusion protein, which acts as a molecular Trojan horse to transport the lysosomal enzymes across the BBB.

ADVANCED DRUG DELIVERY REVIEWS (2022)

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Article Medical Informatics

Application of Meta-analysis to Evaluate Relationships Among ARIA-E Rate, Amyloid Reduction Rate, and Clinical Cognitive Response in Amyloid Therapeutic Clinical Trials for Early Alzheimer's Disease

Deli Wang et al.

Summary: This meta-analysis study found a significant correlation between the removal of β-amyloid plaques in the brain through amyloid therapy and a better clinical response in patients with early Alzheimer's disease, as well as a higher ARIA-E rate.

THERAPEUTIC INNOVATION & REGULATORY SCIENCE (2022)

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Correction Pharmacology & Pharmacy

The Advent of a New Era in Digital Healthcare: A Role for 3D Printing Technologies in Drug Manufacturing? (vol 14, 609, 2022)

Ioannis I. Andreadis et al.

PHARMACEUTICS (2022)

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Editorial Material Medicine, General & Internal

Monoclonal Antibody Therapy in Parkinson's Disease - The End?

Alan Whone

NEW ENGLAND JOURNAL OF MEDICINE (2022)

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Article Medicine, General & Internal

Trial of Prasinezumab in Early-Stage Parkinson's Disease

G. Pagano et al.

Summary: The study found that prasinezumab had no meaningful effect on global or imaging measures of Parkinson's disease progression and was associated with infusion reactions.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

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Article Medicine, General & Internal

Trial of Cinpanemab in Early Parkinson's Disease

A. E. Lang et al.

Summary: In participants with early Parkinson's disease, the effects of cinpanemab on clinical measures of disease progression and changes in DaT-SPECT imaging did not differ from those of placebo over a 52-week period.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

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Article Neurosciences

The Effect of Neuroepo on Cognition in Parkinson's Disease Patients Is Mediated by Electroencephalogram Source Activity

Maria Bringas L. Vega et al.

Summary: This study reports on the quantitative effects of Neuroepo on cognition and electroencephalogram (EEG) in Parkinson's disease (PD). The results show that Neuroepo has a positive influence on cognition in PD patients, and a large portion of this effect is mediated by brain mechanisms reflected in EEG.

FRONTIERS IN NEUROSCIENCE (2022)

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Article Pharmacology & Pharmacy

Brain Delivery of IGF1R5, a Single-Domain Antibody Targeting Insulin-like Growth Factor-1 Receptor

Alvaro Yogi et al.

Summary: The blood-brain barrier (BBB) limits the delivery of drugs and therapeutic antibodies to the central nervous system (CNS). This study investigates receptor-mediated transcytosis (RMT) as a means to increase drug delivery to the brain. IGF1R5, a ligand that triggers RMT, is shown to be able to cross the BBB and deliver cargo molecules. This proof-of-concept study demonstrates the potential of appropriate antibodies as RMT carriers for CNS therapeutic applications.

PHARMACEUTICS (2022)

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Article Pharmacology & Pharmacy

A Single Domain Shark Antibody Targeting the Transferrin Receptor 1 Delivers a TrkB Agonist Antibody to the Brain and Provides Full Neuroprotection in a Mouse Model of Parkinson's Disease

Emily Clarke et al.

Summary: Single domain shark antibodies that bind to the transferrin receptor 1 (TfR1) on brain endothelial cells have been used to shuttle antibodies and other cargos across the blood brain barrier (BBB) to the brain. Fusion of the TXB4 brain shuttle with a TrkB neurotrophin receptor agonist antibody allows the antibody to reach neuroprotective concentrations in the brain parenchyma following systemic administration, showing potent agonist activity at its cognate receptor and preventing the death of dopaminergic neurons in a mouse model of Parkinson's disease.

PHARMACEUTICS (2022)

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Review Pharmacology & Pharmacy

Treatment of Neuronopathic Mucopolysaccharidoses with Blood-Brain Barrier-Crossing Enzymes: Clinical Application of Receptor-Mediated Transcytosis

Hiroyuki Sonoda et al.

Summary: Enzyme replacement therapy (ERT) is effective for somatic symptoms of lysosomal storage diseases (LSDs), but not for central nervous system (CNS)-related symptoms due to the blood-brain barrier (BBB). Efforts have been made to modify enzymes to cross the BBB via receptor-mediated transcytosis (RMT) and treat CNS neuronopathy.

PHARMACEUTICS (2022)

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Article Pharmacology & Pharmacy

Reduction of αSYN Pathology in a Mouse Model of PD Using a Brain-Penetrating Bispecific Antibody

Sahar Roshanbin et al.

Summary: This study investigated a modified bispecific antibody for improved brain uptake in the treatment of Parkinson's disease. The results showed that the antibody could efficiently and quickly penetrate the brain and reduce the aggregation of alpha SYN.

PHARMACEUTICS (2022)

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Article Clinical Neurology

Putaminal Recombinant Glucocerebrosidase Delivery with Magnetic Resonance-Guided Focused Ultrasound in Parkinson's Disease: A Phase I Study

Ying Meng et al.

Summary: This study demonstrates the safety and feasibility of MRgFUS GCase delivery in PD and supports further investigation of this approach.

MOVEMENT DISORDERS (2022)

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Article Biology

Persicaria minor (Huds.) Opiz Prevents In Vitro Atherogenesis by Attenuating Tumor Necrosis Factor-α-Induced Monocyte Adhesion to Human Umbilical Vein Endothelial Cells

Adila A. Hamid et al.

Summary: This in vitro study assessed the protective effects of Persicaria minor leaves extract on monocyte adhesion to human umbilical vein endothelial cells. The results showed that the extract could inhibit adhesion and prevent atherogenesis by inhibiting NF-kappa B activation.

LIFE-BASEL (2022)

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Article Biochemical Research Methods

Grabody B, an IGF1 receptor-based shuttle, mediates efficient delivery of biologics across the blood-brain barrier

Jung-Won Shin et al.

Summary: Effective delivery of therapeutics to the brain remains a challenge. Researchers have identified insulin-like growth factor 1 receptor (IGF1R) as an ideal target for molecular shuttles and developed Grabody B, an antibody that efficiently delivers therapeutics. By fusing with an anti-alpha-synuclein (alpha-Syn) antibody, Grabody B not only improves neuropathology and behavior in a Parkinson's disease animal model, but also exhibits superior serum pharmacokinetics and enhanced brain exposure.

CELL REPORTS METHODS (2022)

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Article Gastroenterology & Hepatology

Incidence of Pancreatic Intraepithelial Neoplasia in an Autopsy Series

Daniel S. Longnecker et al.

Summary: The study aimed to determine the incidence of pancreatic intraepithelial neoplasia (PanIN) in a large group of pancreases obtained at autopsy. The results showed that most pancreases had multiple PanINs, and at least one PanIN was found in 86.4% of the pancreases examined. The study raised questions about the classification and significance of PanIN.

PANCREAS (2022)

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Article Biochemistry & Molecular Biology

TNF-α promotes α-synuclein propagation through stimulation of senescence-associated lysosomal exocytosis

Eun-Jin Bae et al.

Summary: Cell-to-cell propagation of alpha-synuclein, the underlying mechanism of Parkinson's disease, is promoted by the inflammatory cytokine TNF-alpha through stimulation of lysosomal exocytosis. TNF-alpha triggers cellular senescence and increases the secretion of alpha-synuclein, leading to a vicious cycle of inflammation and protein aggregation.

EXPERIMENTAL AND MOLECULAR MEDICINE (2022)

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Review Immunology

Inflammation and immune dysfunction in Parkinson disease

Malu Gamez Tansey et al.

Summary: This review explores the role of an ageing immune system, host genetics, and exposure to environmental stressors in promoting the development of Parkinson's disease. It discusses the presence of neuroinflammation and alterations in immune cell populations as well as the potential contributions of viral or bacterial exposure, pesticides, and gut microbiota to disease pathogenesis.

NATURE REVIEWS IMMUNOLOGY (2022)

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Article Biotechnology & Applied Microbiology

The clinical landscape for AAV gene therapies

Dmitry A. Kuzmin et al.

NATURE REVIEWS DRUG DISCOVERY (2021)

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Article Neurosciences

ABBV-0805, a novel antibody selective for soluble aggregated α-synuclein, prolongs lifespan and prevents buildup of α-synuclein pathology in mouse models of Parkinson's disease

Eva Nordstrom et al.

Summary: ABBV-0805 is a humanized monoclonal antibody with high selectivity for aggregated alpha-synuclein, demonstrating efficacy in cellular and animal models, and showing potential disease-modifying treatment for Parkinson's disease based on strong preclinical findings.

NEUROBIOLOGY OF DISEASE (2021)

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Article Clinical Neurology

Blood-brain barrier permeability in Parkinson's disease patients with and without dyskinesia

Koji Fujita et al.

Summary: In this study, rubidium-82 (Rb-82) PET was used to quantify blood-brain barrier (BBB) permeability in 19 Parkinson's disease (PD) patients, including those with levodopa-induced dyskinesia (LID). The results showed that there were no significant changes in BBB permeability in PD patients, regardless of LID status.

JOURNAL OF NEUROLOGY (2021)

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Review Clinical Neurology

Prodromal Parkinson disease subtypes - key to understanding heterogeneity

Daniela Berg et al.

Summary: Parkinson's disease begins its pathological processes and neurodegeneration long before clinical diagnosis, allowing for identification of individuals likely to develop the disease through risk and prodromal markers. Heterogeneity in clinical and prodromal PD suggests that subtypes exist, differentiated by clinical manifestations, pathomechanisms, and progression patterns. Understanding this variability is crucial for early and accurate diagnosis, as well as for targeting neuroprotective interventions effectively.

NATURE REVIEWS NEUROLOGY (2021)

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Review Neurosciences

Neurotrophic Factors in Parkinson's Disease: Clinical Trials, Open Challenges and Nanoparticle-Mediated Delivery to the Brain

Olesja Bondarenko et al.

Summary: Neurotrophic factors (NTFs) are essential for neuronal development and survival but face challenges in delivery to the brain due to the blood-brain barrier. Nanoparticles (NPs) show promise in stabilizing and transporting NTFs across the BBB, offering a potential solution to systemic delivery.

FRONTIERS IN CELLULAR NEUROSCIENCE (2021)

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Review Neurosciences

An Update on Gene Therapy Approaches for Parkinson's Disease: Restoration of Dopaminergic Function

Amber D. Van Laar et al.

Summary: Gene therapy is an attractive approach to restoring dopamine network function in Parkinson's disease by introducing genetic material. Current PD gene therapy trials are focused on improving dopamine production and/or restoring the nigrostriatal pathway. There are ongoing advancements in study design and surgical approaches.

JOURNAL OF PARKINSONS DISEASE (2021)

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Article Chemistry, Medicinal

Mathematical Models of Blood-Brain Barrier Transport of Monoclonal Antibodies Targeting the Transferrin Receptor and the Insulin Receptor

William M. Pardridge et al.

Summary: This study examines the receptor-mediated transcytosis of monoclonal antibodies targeting transferrin receptor or insulin receptor at the blood-brain barrier, using mathematical models to analyze and predict the transport process. The optimal rates of receptor association with the targeted antibodies are highlighted as crucial factors determining the efficiency of transcytosis.

PHARMACEUTICALS (2021)

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Article Biochemistry & Molecular Biology

Rational engineering of an erythropoietin fusion protein to treat hypoxia

Jungmin Lee et al.

Summary: The fusion protein developed in this study stimulates red blood cell production and neuroprotection, while avoiding thrombosis. It is composed of an anti-glycophorin A nanobody and an erythropoietin mutant. The protein exhibited promising activity in vitro and in mouse models, highlighting its potential as a novel therapeutic molecule for hypoxia.

PROTEIN ENGINEERING DESIGN & SELECTION (2021)

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Article Medicine, General & Internal

Exenatide once weekly over 2 years as a potential disease-modifying treatment for Parkinson's disease: protocol for a multicentre, randomised, double blind, parallel group, placebo controlled, phase 3 trial: The 'Exenatide-PD3' study

Nirosen Vijiaratnam et al.

Summary: The study is a multicenter, double-blind, randomized, placebo-controlled trial in the UK, aiming to confirm the positive effects of exenatide on motor function in patients with moderate Parkinson's disease and to investigate whether effects accumulate with prolonged drug exposure.

BMJ OPEN (2021)

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Review Clinical Neurology

Clinical and Imaging Markers of Prodromal Parkinson's Disease

Eldbjorg Hustad et al.

FRONTIERS IN NEUROLOGY (2020)

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Article Pharmacology & Pharmacy

Brain uptake pharmacokinetics of incretin receptor agonists showing promise as Alzheimer's and Parkinson's disease therapeutics

Therese S. Salameh et al.

BIOCHEMICAL PHARMACOLOGY (2020)

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Article Multidisciplinary Sciences

SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness

Kizzmekia S. Corbett et al.

NATURE (2020)

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Review Neurosciences

GDNF and Parkinson's Disease: Where Next? A Summary from a Recent Workshop

Roger A. Barker et al.

JOURNAL OF PARKINSONS DISEASE (2020)

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Article Multidisciplinary Sciences

COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses

Ugur Sahin et al.

NATURE (2020)

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Article Neurosciences

Erythropoietin modulates striatal antioxidant signalling to reduce neurodegeneration in a toxicant model of Parkinson's disease

A. M. Thompson et al.

MOLECULAR AND CELLULAR NEUROSCIENCE (2020)

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Editorial Material Geriatrics & Gerontology

The Future of GDNF in Parkinson's Disease

Fredric P. Manfredsson et al.

FRONTIERS IN AGING NEUROSCIENCE (2020)

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Article Physiology

Blood-Brain Barrier Leakage Is Increased in Parkinson's Disease

Sarah Al-Bachari et al.

FRONTIERS IN PHYSIOLOGY (2020)

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Review Medicine, General & Internal

GLP-1 receptor agonists for Parkinson's disease

Caroline A. Mulvaney et al.

COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2020)

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Review Neurosciences

Trophic factors for Parkinson's disease: Where are we and where do we go from here?

Gesine Paul et al.

EUROPEAN JOURNAL OF NEUROSCIENCE (2019)

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Review Neurosciences

Impaired dopamine metabolism in Parkinson's disease pathogenesis

Anna Masato et al.

MOLECULAR NEURODEGENERATION (2019)

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Review Neurosciences

The Effects of Leptin on Glial Cells in Neurological Diseases

Yuki Fujita et al.

FRONTIERS IN NEUROSCIENCE (2019)

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Article Biochemistry & Molecular Biology

GDNF-mediated rescue of the nigrostriatal system depends on the degree of degeneration

Luis Quintino et al.

GENE THERAPY (2019)

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Article Neurosciences

Preclinical development of a high affinity α-synuclein antibody, MEDI1341, that can enter the brain, sequester extracellular α-synuclein and attenuate α-synuclein spreading in vivo

Darren J. Schofield et al.

NEUROBIOLOGY OF DISEASE (2019)

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Review Neurosciences

Erythropoietin as a Neuroprotective Molecule: An Overview of Its Therapeutic Potential in Neurodegenerative Diseases

Federica Rey et al.

ASN NEURO (2019)

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Review Neurosciences

Insulin receptor in the brain: Mechanisms of activation and the role in the CNS pathology and treatment

Igor Pomytkin et al.

CNS NEUROSCIENCE & THERAPEUTICS (2018)

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Article Genetics & Heredity

Neurocognitive and somatic stabilization in pediatric patients with severe Mucopolysaccharidosis Type I after 52 weeks of intravenous brain-penetrating insulin receptor antibody-iduronidase fusion protein (valanafusp alpha): an open label phase 1-2 trial

Roberto Giugliani et al.

ORPHANET JOURNAL OF RARE DISEASES (2018)

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Review Rheumatology

20 years of experience with tumour necrosis factor inhibitors: what have we learned?

Roberto Caporali et al.

RHEUMATOLOGY (2018)

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Article Urology & Nephrology

Switching from Epoetin Alfa (Epogen®) to Epoetin Alfa-Epbx (Retacrit™) Using a Specified Dosing Algorithm: A Randomized, Non-Inferiority Study in Adults on Hemodialysis

Ravi Thadhani et al.

AMERICAN JOURNAL OF NEPHROLOGY (2018)

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Article Multidisciplinary Sciences

EPO does not promote interaction between the erythropoietin and beta-common receptors

Karen S. Cheung Tung Shing et al.

SCIENTIFIC REPORTS (2018)

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Article Medicine, Research & Experimental

Interleukin-4 Contributes to Degeneration of Dopamine Neurons in the Lipopolysaccharide-treated Substantia Nigra in vivo

Eugene Bok et al.

EXPERIMENTAL NEUROBIOLOGY (2018)

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Article Clinical Neurology

Levodopa-induced dyskinesia in Parkinson disease A population-based cohort study

Pierpaolo Turcano et al.

NEUROLOGY (2018)

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Article Multidisciplinary Sciences

Carbidopa, a drug in use for management of Parkinson disease inhibits T cell activation and autoimmunity

Huabin Zhu et al.

PLOS ONE (2017)

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Article Biochemistry & Molecular Biology

Isoforms of the Erythropoietin receptor in dopaminergic neurons of the Substantia Nigra

Federica Marcuzzi et al.

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Review Neurosciences

Evaluation of Models of Parkinson's Disease

Shail A. Jagmag et al.

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Article Endocrinology & Metabolism

Expression and Distribution of Glucagon-Like Peptide-1 Receptor mRNA, Protein and Binding in the Male Nonhuman Primate (Macaca mulatta) Brain

Kristy M. Heppner et al.

ENDOCRINOLOGY (2015)

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Generation and characterization of novel conformation-specific monoclonal antibodies for α-synuclein pathology

Nishant N. Vaikath et al.

NEUROBIOLOGY OF DISEASE (2015)

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Review Neurosciences

Neuroinflammation in Parkinson's disease and its potential as therapeutic target

Qinqin Wang et al.

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Charles Pyke et al.

ENDOCRINOLOGY (2014)

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Article Clinical Neurology

Safety and efficacy of recombinant human erythropoietin treatment of non-motor symptoms in Parkinson's disease

Wooyoung Jang et al.

JOURNAL OF THE NEUROLOGICAL SCIENCES (2014)

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Article Neurosciences

Peripheral Administration of the Selective Inhibitor of Soluble Tumor Necrosis Factor (TNF) XPro® 1595 Attenuates Nigral Cell Loss and Glial Activation in 6-OHDA Hemiparkinsonian Rats

Christopher J. Barnum et al.

JOURNAL OF PARKINSONS DISEASE (2014)

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Article Biochemistry & Molecular Biology

The role of tetrahydrobiopterin and catecholamines in the developmental regulation of tyrosine hydroxylase level in the brain

Daigo Homma et al.

JOURNAL OF NEUROCHEMISTRY (2013)

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Article Multidisciplinary Sciences

How insulin engages its primary binding site on the insulin receptor

John G. Menting et al.

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Selective plasma pharmacokinetics and brain uptake in the mouse of enzyme fusion proteins derived from species-specific receptor-targeted antibodies

Qing-Hui Zhou et al.

JOURNAL OF DRUG TARGETING (2012)

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Article Clinical Neurology

Premotor Parkinson's disease: Concepts and definitions

Andrew Siderowf et al.

MOVEMENT DISORDERS (2012)

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Article Multidisciplinary Sciences

A Monoclonal Antibody-GDNF Fusion Protein Is Not Neuroprotective and Is Associated with Proliferative Pancreatic Lesions in Parkinsonian Monkeys

Sachiko Ohshima-Hosoyama et al.

PLOS ONE (2012)

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Article Multidisciplinary Sciences

Allelic Variation in PtGA20Ox Associates with Growth and Wood Properties in Populus spp

Jiaxing Tian et al.

PLOS ONE (2012)

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Article Multidisciplinary Sciences

Targeted Delivery of GDNF through the Blood-Brain Barrier by MRI-Guided Focused Ultrasound

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BRITISH JOURNAL OF PHARMACOLOGY (2011)

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COLD SPRING HARBOR PERSPECTIVES IN MEDICINE (2011)

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Intravenous treatment of experimental Parkinson's disease in the mouse with an IgG-GDNF fusion protein that penetrates the blood-brain barrier

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Monoclonal Antibody-Glial-Derived Neurotrophic Factor Fusion Protein Penetrates the Blood-Brain Barrier in the Mouse

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Selective targeting of a TNFR decoy receptor pharmaceutical to the primate brain as a receptor-specific IgG fusion protein

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Re-Engineering Erythropoietin as an IgG Fusion Protein That Penetrates the Blood-Brain Barrier in the Mouse

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GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism

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GDNF fusion protein for targeted-drug delivery across the human blood-brain barrier

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The Structure of the Glial Cell Line-derived Neurotrophic Factor-Coreceptor Complex INSIGHTS INTO RET SIGNALING AND HEPARIN BINDING

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Intravenous glial-derived neurotrophic factor gene therapy of experimentat Parkinson's disease with Trojan horse liposomes and a tyrosine hydroxylase promoter

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Characterization of the Pharmacokinetics of Human Recombinant Erythropoietin in Blood and Brain When Administered Immediately after Lateral Fluid Percussion Brain Injury and Its Pharmacodynamic Effects on IL-1β and MIP-2 in Rats

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Comparison of cDNA and genomic forms of tyrosine hydroxylase gene therapy of the brain with Trojan horse liposomes

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Intrastriatal administration of erythropoietin protects dopaminergic neurons and improves neurobehavioral outcome in a rat model of Parkinson's disease

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Repetitive vibrissae-elicited forelimb placing before and immediately after unilateral 6-hydroxydopamine improves outcome in a model of Parkinson's disease

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A classical homodimeric erythropoietin receptor is essential for the antiapoptotic effects of erythropoietin on differentiated neuroblastoma SH-SY5Y and pheochromocytoma PC-12 cells

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Erythropoietin does not preserve motor neurons in a mouse model of familial ALS

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Point source concentration of GDNF may explain failure of phase II clinical trial

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Blocking soluble tumor necrosis factor signaling with dominant-negative tumor necrosis factor inhibitor attenuates loss of dopaminergic neurons in models of Parkinson's disease

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Novel agonist monoclonal antibodies activate TrkB receptors and demonstrate potent neurotrophic activities

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Erythropoietin protects against 6-hydroxydopamine-induced dopaminergic cell death

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NATURE REVIEWS NEUROSCIENCE (2006)

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Genetic ablation of tumor necrosis factor-alpha (TNF-α) and pharmacological inhibition of TNF-synthesis attenuates MPTP toxicity in mouse striatum

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Normalization of striatal tyrosine hydroxylase and reversal of motor impairment in experimental parkinsonism with intravenous nonviral gene therapy and a brain-specific promoter

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HUMAN GENE THERAPY (2004)

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Derivatives of erythropoietin that are tissue protective but not erythropoietic

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The involvement of the blood-brain and the blood-cerebrospinal fluid barriers in the distribution of leptin into and out of the rat brain

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Mitogenic effect of glial cell line-derived neurotrophic factor is dependent on the activation of p70S6 kinase, but independent of the activation of ERK and up-regulation of Ret in SH-SY5Y cells

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BRAIN RESEARCH (2003)

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Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2003)

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A rapid assay for glial cell line-derived neurotrophic factor and neurturin based on transfection of cells with tyrosine hydroxylase promoter-luciferase construct

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BRAIN RESEARCH PROTOCOLS (2003)

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Glial cell line-derived neurotrophic factor does not enter normal mouse brain

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NEUROSCIENCE LETTERS (2003)

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NEUROBIOLOGY OF AGING (2003)

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Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD

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Absence of toxicity of chronic weekly intravenous gene therapy with pegylated immunoliposomes

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PHARMACEUTICAL RESEARCH (2003)

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Intravenous nonviral gene therapy causes normalization of striatal tyrosine hydroxylase and reversal of motor impairment in experimental parkinsonism

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HUMAN GENE THERAPY (2003)

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Glial cell line-derived neurotrophic factor up-regulates the expression of tyrosine hydroxylase gene in human neuroblastoma cell lines

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Erythropoietin therapy for acute stroke is both safe and beneficial

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MOLECULAR MEDICINE (2002)

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Differential neuropathological alterations in transgenic mice expressing α-synuclein from the platelet-derived growth factor and Thy-1 promoters

E Rockenstein et al.

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Binding and functional comparisons of two types of tumor necrosis factor antagonists

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Transport of amino acid-related compounds mediated by L-type amino acid transporter 1 (LAT1): Insights into the mechanisms of substrate recognition

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Marked dopaminergic cell loss subsequent to developmental, intranigral expression of glial cell line-derived neurotrophic factor

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EXPERIMENTAL NEUROLOGY (2002)

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Drug and gene targeting to the brain with molecular Trojan horses

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NATURE REVIEWS DRUG DISCOVERY (2002)

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hGFAP-cre transgenic mice for manipulation of glial and neuronal function in vivo

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Evaluation of, dopamine D-2 receptor occupancy by clozapine, risperidone, and haloperidol in vivo in the rodent and nonhuman primate brain using 18F-fallypride

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AMERICAN JOURNAL OF SURGICAL PATHOLOGY (2001)

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The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain barrier

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BRAIN RESEARCH (2000)

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Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2000)

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