Leha, Andreas

[["dc.bibliographiccitation.firstpage","655"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Annals of Clinical and Translational Neurology"],["dc.bibliographiccitation.lastpage","668"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Pringsheim, Milka"],["dc.contributor.author","Mitter, Diana"],["dc.contributor.author","Schröder, Simone"],["dc.contributor.author","Warthemann, Rita"],["dc.contributor.author","Plümacher, Kim"],["dc.contributor.author","Kluger, Gerhard"],["dc.contributor.author","Baethmann, Martina"],["dc.contributor.author","Bast, Thomas"],["dc.contributor.author","Braun, Sarah"],["dc.contributor.author","Büttel, Hans‐Martin"],["dc.contributor.author","Conover, Elizabeth"],["dc.contributor.author","Courage, Carolina"],["dc.contributor.author","Datta, Alexandre N."],["dc.contributor.author","Eger, Angelika"],["dc.contributor.author","Grebe, Theresa A."],["dc.contributor.author","Hasse‐Wittmer, Annette"],["dc.contributor.author","Heruth, Marion"],["dc.contributor.author","Höft, Karen"],["dc.contributor.author","Kaindl, Angela M."],["dc.contributor.author","Karch, Stephanie"],["dc.contributor.author","Kautzky, Torsten"],["dc.contributor.author","Korenke, Georg C."],["dc.contributor.author","Kruse, Bernd"],["dc.contributor.author","Lutz, Richard E."],["dc.contributor.author","Omran, Heymut"],["dc.contributor.author","Patzer, Steffi"],["dc.contributor.author","Philippi, Heike"],["dc.contributor.author","Ramsey, Keri"],["dc.contributor.author","Rating, Tina"],["dc.contributor.author","Rieß, Angelika"],["dc.contributor.author","Schimmel, Mareike"],["dc.contributor.author","Westman, Rachel"],["dc.contributor.author","Zech, Frank‐Martin"],["dc.contributor.author","Zirn, Birgit"],["dc.contributor.author","Ulmke, Pauline A."],["dc.contributor.author","Sokpor, Godwin"],["dc.contributor.author","Tuoc, Tran"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Staudt, Martin"],["dc.contributor.author","Brockmann, Knut"],["dc.date.accessioned","2019-11-25T10:20:06Z"],["dc.date.accessioned","2021-10-27T13:21:31Z"],["dc.date.available","2019-11-25T10:20:06Z"],["dc.date.available","2021-10-27T13:21:31Z"],["dc.date.issued","2019"],["dc.description.abstract","Objective: FOXG1 syndrome is a rare neurodevelopmental disorder associated with heterozygous FOXG1 variants or chromosomal microaberrations in 14q12. The study aimed at assessing the scope of structural cerebral anomalies revealed by neuroimaging to delineate the genotype and neuroimaging phenotype associations. Methods: We compiled 34 patients with a heterozygous (likely) pathogenic FOXG1 variant. Qualitative assessment of cerebral anomalies was performed by standardized re-analysis of all 34 MRI data sets. Statistical analysis of genetic, clinical and neuroimaging data were performed. We quantified clinical and neuroimaging phenotypes using severity scores. Telencephalic phenotypes of adult Foxg1+/- mice were examined using immunohistological stainings followed by quantitative evaluation of structural anomalies. Results: Characteristic neuroimaging features included corpus callosum anomalies (82%), thickening of the fornix (74%), simplified gyral pattern (56%), enlargement of inner CSF spaces (44%), hypoplasia of basal ganglia (38%), and hypoplasia of frontal lobes (29%). We observed a marked, filiform thinning of the rostrum as recurrent highly typical pattern of corpus callosum anomaly in combination with distinct thickening of the fornix as a characteristic feature. Thickening of the fornices was not reported previously in FOXG1 syndrome. Simplified gyral pattern occurred significantly more frequently in patients with early truncating variants. Higher clinical severity scores were significantly associated with higher neuroimaging severity scores. Modeling of Foxg1 heterozygosity in mouse brain recapitulated the associated abnormal cerebral morphology phenotypes, including the striking enlargement of the fornix. Interpretation: Combination of specific corpus callosum anomalies with simplified gyral pattern and hyperplasia of the fornices is highly characteristic for FOXG1 syndrome."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2019"],["dc.identifier.doi","10.1002/acn3.735"],["dc.identifier.eissn","2328-9503"],["dc.identifier.issn","2328-9503"],["dc.identifier.pmid","31019990"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16705"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92029"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","2328-9503"],["dc.relation.issn","2328-9503"],["dc.relation.issn","2328-9503"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.subject.ddc","610"],["dc.title","Structural brain anomalies in patients with FOXG 1 syndrome and in Foxg1+/− mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","293"],["dc.bibliographiccitation.journal","Frontiers in Neurology"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Lingor, Paul"],["dc.contributor.author","Weber, Markus"],["dc.contributor.author","Camu, William"],["dc.contributor.author","Friede, Tim"],["dc.contributor.author","Hilgers, Reinhard"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Neuwirth, Christoph"],["dc.contributor.author","Günther, René"],["dc.contributor.author","Benatar, Michael"],["dc.contributor.author","Kuzma-Kozakiewicz, Magdalena"],["dc.contributor.author","Bidner, Helen"],["dc.contributor.author","Blankenstein, Christiane"],["dc.contributor.author","Frontini, Roberto"],["dc.contributor.author","Ludolph, Albert"],["dc.contributor.author","Koch, Jan C."],["dc.date.accessioned","2019-07-09T11:51:01Z"],["dc.date.available","2019-07-09T11:51:01Z"],["dc.date.issued","2019"],["dc.description.abstract","Objectives: Disease-modifying therapies for amyotrophic lateral sclerosis (ALS) are still not satisfactory. The Rho kinase (ROCK) inhibitor fasudil has demonstrated beneficial effects in cell culture and animal models of ALS. For many years, fasudil has been approved in Japan for the treatment of vasospasm in patients with subarachnoid hemorrhage with a favorable safety profile. Here we describe a clinical trial protocol to repurpose fasudil as a disease-modifying therapy for ALS patients. Methods: ROCK-ALS is a multicenter, double-blind, randomized, placebo-controlled phase IIa trial of fasudil in ALS patients (EudraCT: 2017-003676-31, NCT: 03792490). Safety and tolerability are the primary endpoints. Efficacy is a secondary endpoint and will be assessed by the change in ALSFRS-R, ALSAQ-5, slow vital capacity (SVC), ECAS, and the motor unit number index (MUNIX), as well as survival. Efficacy measures will be assessed before (baseline) and immediately after the infusion therapy as well as on days 90 and 180. Patients will receive a daily dose of either 30 or 60 mg fasudil, or placebo in two intravenous applications for a total of 20 days. Regular assessments of safety will be performed throughout the treatment period, and in the follow-up period until day 180. Additionally, we will collect biological fluids to assess target engagement and evaluate potential biomarkers for disease progression. A total of 120 patients with probable or definite ALS (revised El Escorial criteria) and within 6-18 months of the onset of weakness shall be included in 16 centers in Germany, Switzerland and France. Results and conclusions: The ROCK-ALS trial is a phase IIa trial to evaluate the ROCK-inhibitor fasudil in early-stage ALS-patients that started patient recruitment in 2019."],["dc.identifier.doi","10.3389/fneur.2019.00293"],["dc.identifier.pmid","30972018"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16031"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59859"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","ROCK-ALS: Protocol for a Randomized, Placebo-Controlled, Double-Blind Phase IIa Trial of Safety, Tolerability and Efficacy of the Rho Kinase (ROCK) Inhibitor Fasudil in Amyotrophic Lateral Sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","1800083"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","PROTEOMICS – Clinical Applications"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Masanta, Wycliffe O."],["dc.contributor.author","Zautner, Andreas E."],["dc.contributor.author","Lugert, Raimond"],["dc.contributor.author","Bohne, Wolfgang"],["dc.contributor.author","Gross, Uwe"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Dakna, Mohammed"],["dc.contributor.author","Lenz, Christof"],["dc.date.accessioned","2019-07-09T11:51:53Z"],["dc.date.available","2019-07-09T11:51:53Z"],["dc.date.issued","2018"],["dc.description.abstract","PURPOSE: Bile acids are crucial components of the intestinal antimicrobial defense and represent a significant stress factor for enteric pathogens. Adaptation processes of Campylobacter jejuni to this hostile environment are analyzed in this study by a proteomic approach. EXPERIMENTAL DESIGN: Proteome profiling by label-free mass spectrometry (SWATH-MS) has been used to characterize the adaptation of C. jejuni to sublethal concentrations of seven bile acids. RESULTS: The bile acids with the lowest inhibitory concentration (IC50 ), deoxycholic and chenodeoxycholic acid, induce the most significant proteome changes. Overall a downregulation of all basic biosynthetic pathways and a general decrease in the transcription machinery are found. Concurrently, an induction of factors involved in detoxification of reactive oxygen species, protein folding, and bile acid exporting efflux pumps is detected. Exposure to deoxycholic and chenodeoxycholic acid results in an increased expression of components of the more energy-efficient aerobic respiration pathway, while the anaerobic branches of the electron transport chain are down-expressed. CONCLUSIONS AND CLINICAL RELEVANCE: The results show that C. jejuni has a differentiated system of adaptation to bile acid stresses. The findings enhance the understanding of the pathogenesis of campylobacteriosis, especially for survival of C. jejuni in the human intestine, and may provide clues to future medical treatment."],["dc.identifier.doi","10.1002/prca.201800083"],["dc.identifier.pmid","30246935"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16217"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60032"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Proteome Profiling by Label‐Free Mass Spectrometry Reveals Differentiated Response of Campylobacter jejuni 81–176 to Sublethal Concentrations of Bile Acids"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]