Project Details
Description
In 2007, international collaborations have been established to further investigate the role of astroglial and microglial cells in the initiation and persistence of the inflammatory response associated with neuronal degeneration and hyperexcitability (Grant of the European Union: HEALTH-2007-2.2.1-6:“ Neuron-glia interactions in health and disease”; www.neuroglia.eu ). This has been investigated in human brain and in well established animal models of epilepsy.
2012-2015:. Grant of the European Union: HEALTH.2011.2.2.2-2 " Pathways common to brain development and ageing: defining strategies for preventive therapy and diagnostics “
Objectives
a. To examine neurodegeneration-related proteins during development: comparing early and postnatal developmental stages in developmental disorders
b. To examine the relationship between neurodegeneration-related proteins and specific developmental pathways
c. To study selected altered mRNAs, microRNAs and proteins in focal cortical malformations
2012-2016: Characterization of genetic aberrations in pediatric low-grade glioneuronal tumors Stichting Kinderen Kankervrij (KiKa).
The aim of the study is to identify chromosomal changes in an international large series of GNT’s by genomic wide microarray based comparative genomic hybridization (aCGH), PCR and genomic sequencing. During the project these chromosomal changes will be investigated for their potential clinical relevance as related to prognosis, pathogenesis en epileptogenesis. The miRNA profile of GNT’s will be also evaluated. By investigating these biologic characteristics in relation to the clinical data, we can improve the diagnostics and therapy for GNT’s in children, as guided by the clinical biological risk profile of the tumor.
2013-2017: National Epilepsy Fonds (NEF): miRNA and inflammation: new opportunities for therapy in epilepsy associated pathologies. Recent clinical-neuropathological and experimental observations support the notion that a dysregulation of the astrocyte immune-inflammatory function represents a common factor, which may predispose or directly contribute to the generation of seizures and to seizure-related neuronal damage in epilepsy of various aetiologies.
Since specific miRNAs have been recently shown to regulate the immune/inflammatory responses, our strategy is devoted to identify key miRNAs that may act as regulators of specific pro-inflammatory/ pro-epileptogenic pathways and to study the effects of their modulation and its therapeutic potential in epilepsy, using a multidisciplinary approach.
2013-2017: National Epilepsy Fonds (NEF): Towards effective surgery in focal cortical dysplasias: histopathology, EEG and 7T MRI characteristics. The aim of this proposal is three-fold.First, we want to improve the prediction of postoperative outcome, by elucidating the clinico-pathological correlates of FCD subtypes.
2013-2018: Grant of the European Union: FP7-HEALTH-2013-INNOVATION-(HEALTH.2013.2.2.1-4: Patho-physiology and therapy of epilepsy and epileptiform disorders): “Long-term, prospective study evaluating clinical and molecular biomarkers of epileptogenesis in a genetic model of epilepsy – tuberous sclerosis complex”. EPISTOP.
The aim of EPISTOP is to better understand the pathophysiology of epilepsy and its consequences, to develop a preventative strategy for epilepsy, to identify new biomarkers of epilepsy, and to develop new therapeutic targets to block or otherwise modify epileptogenesis in humans.
To achieve this aim, the risk factors and biomarkers of epilepsy will be identified by a multidisciplinary, systematic approach in three settings:
- a prospective study of epilepsy development in infants with TSC, using a wide range of clinical, neuroimaging, and genetic analyses, including a diverse set of cutting edge analyses of blood samples, that will be obtained at study entry, at the onset of epileptiform discharges on EEG, at seizure onset and at the age of 24 months.
- prospective clinical study of TSC infants treated with antiepileptic drugs at the onset of subclinical seizures in comparison to children treated only after clinical seizures appear, evaluating the benefit of preventative antiepileptic treatment and the possible mechanisms of epilepsy prevention
- analysis of biomarkers of epileptogenesis and drug-resistant epilepsy in epileptogenic brain specimens obtained from patients with TSC who underwent epilepsy surgery and TSC autopsy cases collected in the past.
2013-2018: Grant of the European Union: FP7-HEALTH-2013-INNOVATION-(HEALTH.2013.2.2.1-4: Patho-physiology and therapy of epilepsy and epileptiform disorders): “Targets and biomarkers for antiepileptogenesis”. EPITARGET.
This multi- and transdisciplinary project is therefore focused on the processes leading to epilepsy (i.e. epileptogenesis) in adult brain. Epileptogenesis is a complex multifactorial pathologic process, characterized by the concomitant or sequential occurrence of multiple changes in the brain. A major conceptual originality of this project is to consider the underlying patho-physiologic mechanisms of epileptogenesis as temporally evolving multiple processes, even after the epileptic seizures occur and become recurrent.
Overall scientific objectives of EPITARGET are:
Using multidisciplinary strategies of basic, preclinical and clinical research to:
1. identify novel biomarkers and their combinations that will characterize the different stages of epileptogenesis and predict/diagnose early and late stages of the evolution of the disease.
2. unravel the complex patho-physiology of epileptogenesis and to design new, disease-modifying combinatorial treatment strategies specifically targeted to the different stages of epileptogenesis.
3. translate the knowledge obtained in experimental models to patients in order to improve diagnosis, achieve better patient stratification, and develop new antiepileptogenic treatments and means to predict their efficacy.
Projects 2016:
1. The extracellular matrix in epileptogenesis Innovative Training Networks (ITN) Call: H2020-MSCA-ITN-2014 “ECMED”: (642881; 2015-2018); National Epilepsy Fonds (NEF; 2016-2020).
2. Joint Programme - Neurodegenerative Disease Research ”European research projects for Cross-Disease Analysis of Pathways related to Neurodegenerative Diseases” (2015-2018).
3. Stichting Kinderen Kankervrij (KiKa): Multi-platform analysis of TSC Subependymal Giant Cell Astrocytoma (SEGA) to identify novel therapeutic approaches (2016-2020).
4. Ministero della Salute (sezione Ricerca Sanitaria): Project Type: Italian researcher abroad. PE-2013-02355126: Homer-mGlu5 scaffold as common abnormal mechanism and therapeutic target for Intellectual Disability (ID) and Autism (2016-2019). Theme: Neurological and Psychiatric Disorders
5. 2016-2020: Subsidie Stichting "Michelle" (Tuberous Sclerosis)
6. 2016-2017: Stichting Koppie-AU: MeMo studie Medulloblastoom, moleculaire biologie voor een betere risicoclassificatie bij kinderen .
7. 2017-2021: H2020-MSCA-ITN-2016; EU-GliaPhD: Training, Research and Raising of Public Awareness in Cell Biology and Pathology of Neuroglia (722053)
Societal impact activiteit:
1. Commissielid: International League Against Epilepsy (ILAE)Task Force of the Diagnostic Methods Commission.
2. Tutor/Trekker: neuropathology teaching course aimed at colleagues engaged in the diagnostic evaluation of patients with drug-resistant focal epilepsy. http://www.ilae.org/Visitors/Congress/Ed-INES.cfm
3. Contribution to the 193rd ENMC (European Neuromuscluar center) workshop on pathology diagnosis of idiopathic inflammatory myopathies.
Interview Develage interview: https://www.youtube.com/watch?v=yLvsv3fmER8 Interview ILAE: focal lesions and epilepsy. http://www.ilae.org/Visitors/MeetingProceedings/29thiecvideos.cfm New York Times: New Epilepsy Tactic: Fight Inflammation: http://www.nytimes.com/2012/06/05/health/research/new-epilepsy-tactic-fight-inflammation.html?pagewanted=all&_r=0
Books (2011-2016):
Heidrun Potschka and Eleonora Aronica. Pathophysiology of drug refractoriness. The Atlas of Epilepsies. Springer-Verlag Berlin Heidelberg. DOI: 10.1007/SpringerReference_188157 2011-05-09 09:18:39 UTC, 2011.
Eleonora Aronica and Pitt Niehusmann. Gangliogliomas: molecular pathogenesis and epileptogenesis. Tumors Of The Central Nervous System. Ed. M. A. Hayat, Springer, 2011.
Teresa Ravizza, Silvia Balosso, Eleonora, Aronica, and Annamaria Vezzani. Brain Inflammation and Epilepsy. Epilepsy: Mechanisms, Models and Translational Perspectives., 2010,
Çiğdem Özkara and Eleonora Aronica. Hippocampal sclerosis. Handbook of Clinical Neurology (3rd Series). Elsevier, Handb Clin Neurol.108:621-39, 2012.
Annamaria Vezzani, Stephan Auvin, Teresa Ravizza, Eleonora Aronica Glia-neuronal interactions in ictogenesis and epileptogenesis: role of inflammatory mediators. In: Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, editors. Jasper's Basic Mechanisms of the Epilepsies. 4th edition. Bethesda (MD): National Center for Biotechnology Information (US); 2012
Eleonora Aronica, Werner Stenzel. Reactions of muscle to toxins and drugs. Muscle Disease: Pathology and Genetics - Second Edition. International Society of Neuropathology (ISN) Book Series, 2014.
Clinical Neuroembryology: Development and developmental disorders of the human central nervous system, second edition (2014). Chapter10.7.4 Disorders of Cortical Development and Epilepsy.
Eleonora Aronica and Angelika Mühlebner. Handbook of Clinical Neurology 3rd Series: Neuropathology of Epilepsy (2016).
Eleonora Aronica, Angelika Mühlebner, Erwin van Vliet and Jan GorterModels of Seizure and Epilepsy, Second Edition Technical and methodological issues. Characterization of pathology (2016) .
Nikolay Kuzmin, Sander Idema, Eleonora Aronica, Philip C. de Witt Hamer, Pieter Wesseling, Marie Louise Groot. Higher Harmonic Generation Imaging for NeuroPathology (Taylor & Francis) Neurophotonics (2016).
M. de Visser and E. Aronica. Histopathological Features of Idiopathic Inflammatory Myopathies Myositis (Oxford Rheumatology Library, 2016).
2012-2015:. Grant of the European Union: HEALTH.2011.2.2.2-2 " Pathways common to brain development and ageing: defining strategies for preventive therapy and diagnostics “
Objectives
a. To examine neurodegeneration-related proteins during development: comparing early and postnatal developmental stages in developmental disorders
b. To examine the relationship between neurodegeneration-related proteins and specific developmental pathways
c. To study selected altered mRNAs, microRNAs and proteins in focal cortical malformations
2012-2016: Characterization of genetic aberrations in pediatric low-grade glioneuronal tumors Stichting Kinderen Kankervrij (KiKa).
The aim of the study is to identify chromosomal changes in an international large series of GNT’s by genomic wide microarray based comparative genomic hybridization (aCGH), PCR and genomic sequencing. During the project these chromosomal changes will be investigated for their potential clinical relevance as related to prognosis, pathogenesis en epileptogenesis. The miRNA profile of GNT’s will be also evaluated. By investigating these biologic characteristics in relation to the clinical data, we can improve the diagnostics and therapy for GNT’s in children, as guided by the clinical biological risk profile of the tumor.
2013-2017: National Epilepsy Fonds (NEF): miRNA and inflammation: new opportunities for therapy in epilepsy associated pathologies. Recent clinical-neuropathological and experimental observations support the notion that a dysregulation of the astrocyte immune-inflammatory function represents a common factor, which may predispose or directly contribute to the generation of seizures and to seizure-related neuronal damage in epilepsy of various aetiologies.
Since specific miRNAs have been recently shown to regulate the immune/inflammatory responses, our strategy is devoted to identify key miRNAs that may act as regulators of specific pro-inflammatory/ pro-epileptogenic pathways and to study the effects of their modulation and its therapeutic potential in epilepsy, using a multidisciplinary approach.
2013-2017: National Epilepsy Fonds (NEF): Towards effective surgery in focal cortical dysplasias: histopathology, EEG and 7T MRI characteristics. The aim of this proposal is three-fold.First, we want to improve the prediction of postoperative outcome, by elucidating the clinico-pathological correlates of FCD subtypes.
2013-2018: Grant of the European Union: FP7-HEALTH-2013-INNOVATION-(HEALTH.2013.2.2.1-4: Patho-physiology and therapy of epilepsy and epileptiform disorders): “Long-term, prospective study evaluating clinical and molecular biomarkers of epileptogenesis in a genetic model of epilepsy – tuberous sclerosis complex”. EPISTOP.
The aim of EPISTOP is to better understand the pathophysiology of epilepsy and its consequences, to develop a preventative strategy for epilepsy, to identify new biomarkers of epilepsy, and to develop new therapeutic targets to block or otherwise modify epileptogenesis in humans.
To achieve this aim, the risk factors and biomarkers of epilepsy will be identified by a multidisciplinary, systematic approach in three settings:
- a prospective study of epilepsy development in infants with TSC, using a wide range of clinical, neuroimaging, and genetic analyses, including a diverse set of cutting edge analyses of blood samples, that will be obtained at study entry, at the onset of epileptiform discharges on EEG, at seizure onset and at the age of 24 months.
- prospective clinical study of TSC infants treated with antiepileptic drugs at the onset of subclinical seizures in comparison to children treated only after clinical seizures appear, evaluating the benefit of preventative antiepileptic treatment and the possible mechanisms of epilepsy prevention
- analysis of biomarkers of epileptogenesis and drug-resistant epilepsy in epileptogenic brain specimens obtained from patients with TSC who underwent epilepsy surgery and TSC autopsy cases collected in the past.
2013-2018: Grant of the European Union: FP7-HEALTH-2013-INNOVATION-(HEALTH.2013.2.2.1-4: Patho-physiology and therapy of epilepsy and epileptiform disorders): “Targets and biomarkers for antiepileptogenesis”. EPITARGET.
This multi- and transdisciplinary project is therefore focused on the processes leading to epilepsy (i.e. epileptogenesis) in adult brain. Epileptogenesis is a complex multifactorial pathologic process, characterized by the concomitant or sequential occurrence of multiple changes in the brain. A major conceptual originality of this project is to consider the underlying patho-physiologic mechanisms of epileptogenesis as temporally evolving multiple processes, even after the epileptic seizures occur and become recurrent.
Overall scientific objectives of EPITARGET are:
Using multidisciplinary strategies of basic, preclinical and clinical research to:
1. identify novel biomarkers and their combinations that will characterize the different stages of epileptogenesis and predict/diagnose early and late stages of the evolution of the disease.
2. unravel the complex patho-physiology of epileptogenesis and to design new, disease-modifying combinatorial treatment strategies specifically targeted to the different stages of epileptogenesis.
3. translate the knowledge obtained in experimental models to patients in order to improve diagnosis, achieve better patient stratification, and develop new antiepileptogenic treatments and means to predict their efficacy.
Projects 2016:
1. The extracellular matrix in epileptogenesis Innovative Training Networks (ITN) Call: H2020-MSCA-ITN-2014 “ECMED”: (642881; 2015-2018); National Epilepsy Fonds (NEF; 2016-2020).
2. Joint Programme - Neurodegenerative Disease Research ”European research projects for Cross-Disease Analysis of Pathways related to Neurodegenerative Diseases” (2015-2018).
3. Stichting Kinderen Kankervrij (KiKa): Multi-platform analysis of TSC Subependymal Giant Cell Astrocytoma (SEGA) to identify novel therapeutic approaches (2016-2020).
4. Ministero della Salute (sezione Ricerca Sanitaria): Project Type: Italian researcher abroad. PE-2013-02355126: Homer-mGlu5 scaffold as common abnormal mechanism and therapeutic target for Intellectual Disability (ID) and Autism (2016-2019). Theme: Neurological and Psychiatric Disorders
5. 2016-2020: Subsidie Stichting "Michelle" (Tuberous Sclerosis)
6. 2016-2017: Stichting Koppie-AU: MeMo studie Medulloblastoom, moleculaire biologie voor een betere risicoclassificatie bij kinderen .
7. 2017-2021: H2020-MSCA-ITN-2016; EU-GliaPhD: Training, Research and Raising of Public Awareness in Cell Biology and Pathology of Neuroglia (722053)
Societal impact activiteit:
1. Commissielid: International League Against Epilepsy (ILAE)Task Force of the Diagnostic Methods Commission.
2. Tutor/Trekker: neuropathology teaching course aimed at colleagues engaged in the diagnostic evaluation of patients with drug-resistant focal epilepsy. http://www.ilae.org/Visitors/Congress/Ed-INES.cfm
3. Contribution to the 193rd ENMC (European Neuromuscluar center) workshop on pathology diagnosis of idiopathic inflammatory myopathies.
Interview Develage interview: https://www.youtube.com/watch?v=yLvsv3fmER8 Interview ILAE: focal lesions and epilepsy. http://www.ilae.org/Visitors/MeetingProceedings/29thiecvideos.cfm New York Times: New Epilepsy Tactic: Fight Inflammation: http://www.nytimes.com/2012/06/05/health/research/new-epilepsy-tactic-fight-inflammation.html?pagewanted=all&_r=0
Books (2011-2016):
Heidrun Potschka and Eleonora Aronica. Pathophysiology of drug refractoriness. The Atlas of Epilepsies. Springer-Verlag Berlin Heidelberg. DOI: 10.1007/SpringerReference_188157 2011-05-09 09:18:39 UTC, 2011.
Eleonora Aronica and Pitt Niehusmann. Gangliogliomas: molecular pathogenesis and epileptogenesis. Tumors Of The Central Nervous System. Ed. M. A. Hayat, Springer, 2011.
Teresa Ravizza, Silvia Balosso, Eleonora, Aronica, and Annamaria Vezzani. Brain Inflammation and Epilepsy. Epilepsy: Mechanisms, Models and Translational Perspectives., 2010,
Çiğdem Özkara and Eleonora Aronica. Hippocampal sclerosis. Handbook of Clinical Neurology (3rd Series). Elsevier, Handb Clin Neurol.108:621-39, 2012.
Annamaria Vezzani, Stephan Auvin, Teresa Ravizza, Eleonora Aronica Glia-neuronal interactions in ictogenesis and epileptogenesis: role of inflammatory mediators. In: Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, editors. Jasper's Basic Mechanisms of the Epilepsies. 4th edition. Bethesda (MD): National Center for Biotechnology Information (US); 2012
Eleonora Aronica, Werner Stenzel. Reactions of muscle to toxins and drugs. Muscle Disease: Pathology and Genetics - Second Edition. International Society of Neuropathology (ISN) Book Series, 2014.
Clinical Neuroembryology: Development and developmental disorders of the human central nervous system, second edition (2014). Chapter10.7.4 Disorders of Cortical Development and Epilepsy.
Eleonora Aronica and Angelika Mühlebner. Handbook of Clinical Neurology 3rd Series: Neuropathology of Epilepsy (2016).
Eleonora Aronica, Angelika Mühlebner, Erwin van Vliet and Jan GorterModels of Seizure and Epilepsy, Second Edition Technical and methodological issues. Characterization of pathology (2016) .
Nikolay Kuzmin, Sander Idema, Eleonora Aronica, Philip C. de Witt Hamer, Pieter Wesseling, Marie Louise Groot. Higher Harmonic Generation Imaging for NeuroPathology (Taylor & Francis) Neurophotonics (2016).
M. de Visser and E. Aronica. Histopathological Features of Idiopathic Inflammatory Myopathies Myositis (Oxford Rheumatology Library, 2016).
| Status | Active |
|---|---|
| Effective start/end date | 1/05/2007 → … |