Research Topics
| Detlev BoisonSummaryAffiliation: Legacy Research Country: USA Publications
Research Grants
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Publications
Modulators of nucleoside metabolism in the therapy of brain diseasesDetlev Boison
RS Dow Neurobiology Laboratories, Legacy Research, 1225 NE 2nd Ave, Portland, OR 97232, USA
Curr Top Med Chem 11:1068-86. 2011..Finally, novel gene-based therapeutic strategies to inhibit nucleoside metabolism and focal treatment approaches will be discussed...
Adenosine kinase: exploitation for therapeutic gainDetlev Boison
Legacy Research Institute, 1225 NE 16th Ave, Portland, OR 97202
Pharmacol Rev 65:906-43. 2013..Challenges to translate ADK-based therapies into clinical use will be discussed critically...- Adenosine dysfunction in epilepsyDetlev Boison
R S Dow Neurobiology Labs, Legacy Research Institute, Portland, Oregon 97232, USA
Glia 60:1234-43. 2012..Thus, ADK emerges as a promising target for the prediction and prevention of epilepsy... - Adenosine hypothesis of schizophrenia--opportunities for pharmacotherapyDetlev Boison
Robert Stone Dow Neurobiology Laboratories, Legacy Research Institute, 1225 NE 2nd Avenue, Portland, OR 97232, USA
Neuropharmacology 62:1527-43. 2012..Key preliminary clinical data and preclinical findings are reviewed... 
Adenosine kinase, epilepsy and stroke: mechanisms and therapiesDetlev Boison
R S Dow Neurobiology Laboratories, Legacy Research, Portland, OR 97202, USA
Trends Pharmacol Sci 27:652-8. 2006..A new era of cell-based delivery of adenosine has begun, which holds great promise for novel therapies for epilepsy and stroke...- The adenosine kinase hypothesis of epileptogenesisDetlev Boison
R S Dow Neurobiology Laboratories, Legacy Research, Portland, OR 97232, USA
Prog Neurobiol 84:249-62. 2008..iv) Intrahippocampal implants of stem cells engineered to lack ADK prevent epileptogenesis. Thus, ADK emerges both as a diagnostic marker to predict, as well as a prime therapeutic target to prevent, epileptogenesis... - Adenosine as a modulator of brain activityDetlev Boison
R S Dow Neurobiology Laboratories, Portland, Oregon 97232, USA
Drug News Perspect 20:607-11. 2007..Thus, adenosine-based therapies are rapidly evolving in preclinical and clinical studies... - Engineered adenosine-releasing cells for epilepsy therapy: human mesenchymal stem cells and human embryonic stem cellsDetlev Boison
R S Dow Neurobiology Laboratories, Legacy Research, Portland, Oregon 97232, USA
Neurotherapeutics 6:278-83. 2009..Using the same lentiviral micro-RNA vector, we demonstrated knockdown of ADK in hESCs. New developments and therapeutic challenges in using human mesenchymal stem cells and hESCs for epilepsy therapy will be critically evaluated... - Adenosine augmentation therapies (AATs) for epilepsy: prospect of cell and gene therapiesDetlev Boison
Robert Stone Dow Neurobiology Laboratories, Legacy Research, 1225 NE 2nd Ave, Portland, OR 97232, USA
Epilepsy Res 85:131-41. 2009..New developments and therapeutic challenges in using AATs for epilepsy therapy will critically be evaluated... - Adenosine-based cell therapy approaches for pharmacoresistant epilepsiesDetlev Boison
NCCR Neural Plasticity and Repair, University and ETH Zurich, Zurich, Switzerland
Neurodegener Dis 4:28-33. 2007..This review summarizes the rationale and recent approaches for adenosine-based cell therapies for pharmacoresistant epilepsies... - Therapeutic epilepsy research: from pharmacological rationale to focal adenosine augmentationDetlev Boison
Robert Stone Dow Neurobiology Laboratories, Legacy Research, Portland, OR 97232, USA
Biochem Pharmacol 78:1428-37. 2009..Finally, new developments and therapeutic challenges in using focal AATs for epilepsy therapy will critically be evaluated... - Adenosine signaling and function in glial cellsD Boison
Robert Stone Dow Neurobiology Laboratories, Legacy Research, Portland, OR 97232, USA
Cell Death Differ 17:1071-82. 2010..Eventually, glial adenosine-modulating drug targets might be an attractive alternative for the treatment of neurodegenerative diseases. There are, however, several major open questions that remain to be tackled... - Inhibitory RNA in epilepsy: research tools and therapeutic perspectivesDetlev Boison
Robert Stone Dow Neurobiology Laboratories, Legacy Research, Portland, Oregon 97232, USA
Epilepsia 51:1659-68. 2010..Technical issues and challenges remain before those promising tools can be developed into future therapeutics for epilepsy... - Adenosine as a neuromodulator in neurological diseasesDetlev Boison
Legacy Research, R S Dow Neurobiology Laboratories, 1225 NE 2nd Avenue, Portland, OR 97232, USA
Curr Opin Pharmacol 8:2-7. 2008..A new era of adenosine-based therapies has begun, with the prospect to cover a wide range of neurological diseases... - Adenosine augmentation ameliorates psychotic and cognitive endophenotypes of schizophreniaHai Ying Shen
Robert Stone Dow Neurobiology Laboratories, Legacy Research Institute, Portland, OR, USA
J Clin Invest 122:2567-77. 2012.... - Antiepileptic effects of silk-polymer based adenosine release in kindled ratsCory Szybala
Robert S Dow Neurobiology Laboratories, Legacy Research, 1225 NE 2nd Avenue, Portland, OR 97232, USA
Exp Neurol 219:126-35. 2009..We conclude that silk-based adenosine delivery exerts potent anti-ictogenic effects, but might also have at least partial anti-epileptogenic effects. Thus, silk-based adenosine augmentation holds promise for the treatment of epilepsy... - Human mesenchymal stem cell grafts engineered to release adenosine reduce chronic seizures in a mouse model of CA3-selective epileptogenesisTianfu Li
Robert Stone Dow Neurobiology Laboratories, Legacy Research, 1225 NE 2nd Avenue, Portland, OR 97232, USA
Epilepsy Res 84:238-41. 2009..Here we demonstrate reduction of chronic seizures in a mouse model of CA3-selective epileptogenesis after infrahippocampal transplantation of adenosine-releasing hMSCs... - Local disruption of glial adenosine homeostasis in mice associates with focal electrographic seizures: a first step in epileptogenesis?Tianfu Li
Robert S Dow Neurobiology Laboratories, Legacy Research Institute, Portland, Oregon 97232, USA
Glia 60:83-95. 2012..A secondary event, here mimicked by brain-wide disruption of adenosine signaling, is likely required to turn pre-existing subclinical seizures into a clinical seizure phenotype... - Adenosine kinase is a target for the prediction and prevention of epileptogenesis in miceTianfu Li
Robert S Dow Neurobiology Laboratories, Legacy Clinical Research, Portland, Oregon 97232, USA
J Clin Invest 118:571-82. 2008..Our findings suggest that astrocyte-based ADK provides a critical link between astrogliosis and neuronal dysfunction in epilepsy... - Downregulation of hippocampal adenosine kinase after focal ischemia as potential endogenous neuroprotective mechanismGiuseppe Pignataro
Robert S Dow Neurobiology Laboratories, Legacy Research, Portland, Oregon 97232, USA
J Cereb Blood Flow Metab 28:17-23. 2008..Thus, transient downregulation of hippocampal ADK after stroke might be a protective mechanism during maturation hippocampal cell loss... - Uncoupling of astrogliosis from epileptogenesis in adenosine kinase (ADK) transgenic miceTianfu Li
R S Dow Neurobiology Laboratories, Portland, OR 97232, USA
Neuron Glia Biol 4:91-9. 2008..By uncoupling ADK-expression from astrogliosis, we demonstrate that global expression levels of ADK rather than astrogliosis per se contribute to seizure generation... - A novel mouse model for sudden unexpected death in epilepsy (SUDEP): role of impaired adenosine clearanceHai Ying Shen
Robert Stone Dow Neurobiology Laboratories, Legacy Research, Portland, Oregon 97232, USA
Epilepsia 51:465-8. 2010..75 +/- 1.35 min to 54.86 +/- 6.59 min (p < 0.01). Our data indicate that SUDEP is due to overactivation of adenosine receptors and that caffeine treatment after seizure onset might be beneficial... - Lentiviral RNAi-induced downregulation of adenosine kinase in human mesenchymal stem cell grafts: a novel perspective for seizure controlGaoying Ren
Robert S Dow Neurobiology Laboratories, Legacy Research, 1225 NE 2nd Avenue, Portland, OR 97232, USA
Exp Neurol 208:26-37. 2007.... - Adenosine kinase determines the degree of brain injury after ischemic stroke in miceHai Ying Shen
Robert Stone Dow Neurobiology Laboratories, Legacy Research Institute, Portland, Oregon 97232, USA
J Cereb Blood Flow Metab 31:1648-59. 2011..Together, our data define ADK as a possible therapeutic target for modulating the degree of stroke-induced brain injury... - Adenosine kinase as a target for therapeutic antisense strategies in epilepsyPanos Theofilas
RS Dow Neurobiology Laboratories, Legacy Research, Portland, Oregon 97232, USA
Epilepsia 52:589-601. 2011..Here we validate adenosine kinase (ADK), the astrocyte-based key negative regulator of the brain's endogenous anticonvulsant adenosine, as a potential therapeutic target for antisense-mediated seizure suppression... - Neuroprotection in ischemic mouse brain induced by stem cell-derived brain implantsGiuseppe Pignataro
Robert S Dow Neurobiology Laboratories, Legacy Research, Portland, Oregon 97232, USA
J Cereb Blood Flow Metab 27:919-27. 2007..We conclude that ES cell derived adenosine-releasing brain implants provide neuroprotection by synergism of endogenous precursor cell-mediated effects and paracrine adenosine release... - Suppression of kindling epileptogenesis by adenosine releasing stem cell-derived brain implantsTianfu Li
R S Dow Neurobiology Laboratories, Legacy Research, 1225 NE 2nd Ave, Portland, OR 97232, USA
Brain 130:1276-88. 2007..These findings may indicate a potential antiepileptogenic function of stem cell-mediated adenosine delivery... - Glycine transporter 1 as a potential therapeutic target for schizophrenia-related symptoms: evidence from genetically modified mouse models and pharmacological inhibitionHanns Mohler
Institute of Pharmacology, University and ETH Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
Biochem Pharmacol 81:1065-77. 2011..Thus, interventions at GlyT1 are highly effective in modifying multiple brain functions, and dissection of their respective mechanisms is expected to further maximize their therapeutic potential for human mental diseases... - Transgenic overexpression of adenosine kinase aggravates cell death in ischemiaGiuseppe Pignataro
Robert S Dow Neurobiology Laboratories, Legacy Research, Portland, Oregon 97232, USA
J Cereb Blood Flow Metab 27:1-5. 2007..We conclude that pathologic overexpression of ADK as in epilepsy may also render the brain more susceptible to injury from ischemia. Consequently, ADK emerges as a rational therapeutic target to enhance neuroprotection... - Silk polymer-based adenosine release: therapeutic potential for epilepsyAndrew Wilz
Robert Stone Dow Neurobiology Laboratories, Legacy Research, 1225 NE 2nd Avenue, Portland, OR 97232, USA
Biomaterials 29:3609-16. 2008..Histological analysis of brain samples confirmed the correct location of implants and electrodes. We conclude that silk-based delivery of around 1000ng adenosine per day is a safe and efficient strategy to suppress seizures... - Suppression of kindled seizures by paracrine adenosine release from stem cell-derived brain implantsMartin Güttinger
Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland
Epilepsia 46:1162-9. 2005..The aim of the present study was to investigate the potential of differentiated Adk-/- ES cell progeny for seizure suppression by paracrine adenosine release... - Caffeine prevents acute mortality after TBI in rats without increased morbidityTheresa A Lusardi
Robert Stone Dow Neurobiology Laboratories, Legacy Research Institute, Portland, OR 97232, USA
Exp Neurol 234:161-8. 2012..Further, we show epileptiform bursting is reduced after caffeine treatment, suggesting a potential role in the modulation of epilepsy development after severe injury... - Deletion of striatal adenosine A(2A) receptor spares latent inhibition and prepulse inhibition but impairs active avoidance learningPhilipp Singer
Laboratory of Behavioral Neurobiology, ETH Zurich, Schorenstrasse 16, 8603 Schwerzenbach, Switzerland Robert Stone Dow Neurobiology Laboratories, Legacy Research Institute, 1225 NE Second Avenue, Portland, OR 97232, USA Electronic address
Behav Brain Res 242:54-61. 2013.... - Regulation of cognition and symptoms of psychosis: focus on GABA(A) receptors and glycine transporter 1Hanns Mohler
University of Zurich and Swiss Federal Institute of Technology, Zurich, Institute of Pharmacology, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
Pharmacol Biochem Behav 90:58-64. 2008..Taken together, these results qualify distinct GABA-A receptor subtypes and GlyT1 as molecular targets for the development of a new pharmacology in the treatment of cognitive decline and psychotic symptoms... - Adenosine and epilepsy: from therapeutic rationale to new therapeutic strategiesDetlev Boison
Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland
Neuroscientist 11:25-36. 2005..Adenosine-releasing cells or devices implanted into or near a seizure focus offer new hopes for a side effect-free therapy for pharmacoresistant epilepsy... - The use of real-time PCR with fluorogenic probes for the rapid selection of mutant neuroectodermal graftsValérie Zumsteg
Institute of Pharmacology and Toxicology, University of Zurich, CH 8057, Zurich, Switzerland
J Neurosci Methods 120:85-94. 2002..The method described here suggests the feasibility to graft adenosine releasing neuroectodermal cells as a potential therapeutic approach for the treatment of pharmacoresistant epilepsy... - The support of adenosine release from adenosine kinase deficient ES cells by silk substratesLorenz Uebersax
Institute for Pharmaceutical Sciences, Drug Formulation and Delivery, ETH Zurich, CH 8093 Zurich, Switzerland
Biomaterials 27:4599-607. 2006..Taken together, these results suggest that silk matrices are particularly suitable biomaterials for ESC encapsulation and for the design of adenosine releasing bioincubators for the treatment of epilepsy... - Amino acid composition of brain cysts: levels of excitatory amino acids in cyst fluid fail to predict seizuresHeinz Gregor Wieser
Department of Neurology, University Hospital, University of Zurich, Frauenklinikstrasse 26, CH 8091 Zurich, Switzerland
Epilepsy Res 55:191-9. 2003..In summary, there is no evidence for a close correlation between excitatory amino acids in brain cysts and the occurrence of seizures... - Overexpression of adenosine kinase in epileptic hippocampus contributes to epileptogenesisNicolette Gouder
Institute of Pharmacology and Toxicology, University of Zurich, CH 8057 Zurich, Switzerland
J Neurosci 24:692-701. 2004..We conclude that overexpression of adenosine kinase in discrete parts of the epileptic hippocampus may contribute to the development and progression of seizure activity... - Seizure suppression and lack of adenosine A1 receptor desensitization after focal long-term delivery of adenosine by encapsulated myoblastsMartin Güttinger
Institute of Pharmacology and Toxicology, University of Zurich, CH 8057 Zurich, Switzerland
Exp Neurol 193:53-64. 2005..Thus, the local release of adenosine by cellular implants provides a feasible option for a potential side-effect free approach for the long-term treatment of focal epilepsies... - Seizure suppression by adenosine A(2A) receptor activation in a rat model of audiogenic brainstem epilepsyAlexander Huber
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
Neurosci Lett 329:289-92. 2002.... - Seizure suppression by adenosine-releasing cells is independent of seizure frequencyDetlev Boison
Institute of Pharmacology and Toxicology, University of Zurich, Switzerland
Epilepsia 43:788-96. 2002..We tested whether the suppression of seizures by adenosine-releasing grafts was independent of seizure frequency... - entla, a novel epileptic and ataxic Cacna2d2 mutant of the mouseJulia Brill
Institut fur Biochemie, Emil Fischer Zentrum, Friedrich Alexander Universitat Erlangen Nurnberg, D 91054 Erlangen, Germany
J Biol Chem 279:7322-30. 2004..entla is allelic to ducky and ducky2J, representing the third murine Cacna2d2 allele identified and so far the only one encoding an untruncated protein that is incorporated into membranes... - Seizure suppression by adenosine A1 receptor activation in a mouse model of pharmacoresistant epilepsyNicolette Gouder
Institute of Pharmacology and Toxicology, University of Zurich, Switzerland
Epilepsia 44:877-85. 2003..We conclude that the local delivery of adenosine into the brain is likely to be effective in the control of intractable seizures... - Engineering embryonic stem cell derived glia for adenosine deliveryDenise E Fedele
Institute of Pharmacology and Toxicology, , , Switzerland
Neurosci Lett 370:160-5. 2004..1 +/- 6.0 ng per 10(5) cells per hour, an amount considered to be sufficient for seizure suppression. Our findings indicate that Adk-/- ES cells constitute a potential source for therapeutic adenosine releasing grafts... - A critical role of the adenosine A2A receptor in extrastriatal neurons in modulating psychomotor activity as revealed by opposite phenotypes of striatum and forebrain A2A receptor knock-outsHai Ying Shen
Molecular Neuropharmacology Laboratory, Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, USA
J Neurosci 28:2970-5. 2008..These results indicate that A(2A)Rs in striatal and extrastriatal neurons exert an opposing modulation of psychostimulant effects and provide the first direct demonstration of a predominant facilitatory role of extrastriatal A(2A)Rs... - Astrogliosis in epilepsy leads to overexpression of adenosine kinase, resulting in seizure aggravationDenise E Fedele
Institute of Pharmacology and Toxicology, University of Zurich, Switzerland
Brain 128:2383-95. 2005..We therefore conclude that therapeutic strategies that augment the adenosine system after astrogliosis-induced upregulation of ADK constitute a neurochemical rationale for the prevention of seizures in epilepsy... - Neonatal hepatic steatosis by disruption of the adenosine kinase geneDetlev Boison
Institute of Pharmacology and Toxicology, University of Zurich, CH 8057 Zurich, Switzerland
Proc Natl Acad Sci U S A 99:6985-90. 2002..Thus, a deficiency in adenosine metabolism is identified as a powerful contributor to the development of neonatal hepatic steatosis, providing a model for the rapid development of postnatally lethal fatty liver... - Disruption of glycine transporter 1 restricted to forebrain neurons is associated with a procognitive and antipsychotic phenotypic profileBenjamin K Yee
Laboratory of Behavioral Neurobiology, Swiss Federal Institute of Technology, 8603 Schwerzenbach, Switzerland
J Neurosci 26:3169-81. 2006.... - Transgenic overexpression of adenosine kinase in brain leads to multiple learning impairments and altered sensitivity to psychomimetic drugsBenjamin K Yee
Laboratory of Behavioral Neurobiology, Swiss Federal Institute of Technology Zurich, Schwerzenbach, Switzerland
Eur J Neurosci 26:3237-52. 2007..The present findings are of relevance to current pathophysiological hypotheses of schizophrenia and its pharmacotherapy... - Adenosine A1 receptors are crucial in keeping an epileptic focus localizedDenise E Fedele
Institute of Pharmacology and Toxicology, University of Zurich, CH 8057 Zurich, Switzerland
Exp Neurol 200:184-90. 2006..These results open up a new dimension of the A1 receptor's role in controlling excitotoxic cell death and further demonstrate its importance in preventing the progression of status epilepticus to lethal consequences...
Research Grants
- Adenosine and schizophrenia: mechanisms and therapiesDetlev Boison; Fiscal Year: 2010....
- Astrocyte dysfunction in epileptogenesis: the role of adenosineDetlev Boison; Fiscal Year: 2009....
- Adenosine and schizophrenia: mechanisms and therapiesDetlev Boison; Fiscal Year: 2009....
- Adenosine-releasing brain implants for epilepsy therapyDetlev Boison; Fiscal Year: 2010..Our SPECIFIC AIMS are: Aim 1. Engineer biocompatible polymers for the local therapeutic delivery of adenosine. Aim 2. Develop a polymer/cell based system for the sustained delivery of adenosine. ..
- Astrocyte dysfunction in epileptogenesis: the role of adenosineDetlev Boison; Fiscal Year: 2010....
- Adenosine-releasing brain implants for epilepsy therapyDetlev Boison; Fiscal Year: 2011..Our SPECIFIC AIMS are: Aim 1. Engineer biocompatible polymers for the local therapeutic delivery of adenosine. Aim 2. Develop a polymer/cell based system for the sustained delivery of adenosine. ..