0000000001320724

AUTHOR

Markus Glatzel

showing 4 related works from this author

Severe meningo-/encephalitis after daclizumab therapy for multiple sclerosis.

2019

Background: Daclizumab is a monoclonal antibody that binds the high-affinity interleukin-2 receptor and was approved for the treatment of relapsing multiple sclerosis. Due to severe inflammatory brain disorders, the approval was suspended in March 2018. Objective and Methods: This retrospective cohort study summarizes clinical, laboratory, radiological, and histological findings of seven patients who developed meningo-/encephalitis after daclizumab therapy. Results: Patients presented with encephalitis and/or meningitis and suffered from systemic symptoms such as fever (5/7), exanthema (5/7), or gastrointestinal symptoms (4/7). Secondary autoimmune diseases developed. Blood analysis reveale…

AdultMaleDaclizumabMultiple Sclerosismedicine.drug_classMonoclonal antibodyAutoimmune Diseases03 medical and health sciences0302 clinical medicineDaclizumabmedicineHumansLymphocytes030304 developmental biologyRetrospective Studies0303 health sciencesbusiness.industryMultiple sclerosisMeningoencephalitisAntibodies MonoclonalBrainMiddle Agedmedicine.disease3. Good healthNeurologyImmunologyEncephalitisFemaleNeurology (clinical)business030217 neurology & neurosurgeryEncephalitisImmunosuppressive Agentsmedicine.drugMultiple sclerosis (Houndmills, Basingstoke, England)
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RNase H2 Loss in Murine Astrocytes Results in Cellular Defects Reminiscent of Nucleic Acid-Mediated Autoinflammation

2018

Aicardi-Goutières syndrome (AGS) is a rare early onset childhood encephalopathy caused by persistent neuroinflammation of autoimmune origin. AGS is a genetic disorder and >50% of affected individuals bear hypomorphic mutations in ribonuclease H2 (RNase H2). All available RNase H2 mouse models so far fail to mimic the prominent CNS involvement seen in AGS. To establish a mouse model recapitulating the human disease, we deleted RNase H2 specifically in the brain, the most severely affected organ in AGS. Although RNase H2δGFAPmice lacked the nuclease in astrocytes and a majority of neurons, no disease signs were apparent in these animals. We additionally confirmed these results…

0301 basic medicinelcsh:Immunologic diseases. AllergyMaleEncephalomyelitis Autoimmune ExperimentalAicardi–Goutières syndromeRNase PDNA damageImmunologyRibonuclease HFluorescent Antibody TechniqueAicardi-goutières Syndrome ; Cellular Senescence ; Dna Damage ; Interferon Signature ; Rnase H2BiologyNervous System MalformationsAutoimmune Diseases03 medical and health sciencesMiceAutoimmune Diseases of the Nervous SystemNucleic AcidsmedicineImmunology and Allergycellular senescenceAnimalsRibonucleaseNeuroinflammationCells CulturedOriginal ResearchInflammationMice KnockoutInnate immune systemBrainmedicine.diseaseMolecular biologyImmunohistochemistryDisease Models Animal030104 developmental biologymedicine.anatomical_structurePhenotypeinterferon signatureAstrocytesKnockout mousebiology.proteinAicardi–Goutières syndromeDNA damageFemalelcsh:RC581-607RNase H2BiomarkersAstrocyteFrontiers in Immunology
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Enzyme replacement therapy with recombinant pro-CTSD (cathepsin D) corrects defective proteolysis and autophagy in neuronal ceroid lipofuscinosis

2019

CTSD (cathepsin D) is one of the major lysosomal proteases indispensable for the maintenance of cellular proteostasis by turning over substrates of endocytosis, phagocytosis and autophagy. Consequently, CTSD deficiency leads to a strong impairment of the lysosomal-autophagy machinery. In mice and humans CTSD dysfunction underlies the congenital variant (CLN10) of neuronal ceroid lipofuscinosis (NCL). NCLs are distinct lysosomal storage disorders (LSDs) sharing various hallmarks, namely accumulation of protein aggregates and ceroid lipofuscin leading to neurodegeneration and blindness. The most established and clinically approved approach to treat LSDs is enzyme replacement therapy (ERT) aim…

0301 basic medicineproteolysisCathepsin DCathepsin DCathepsin BstorageCathepsin L03 medical and health sciencesSequestosome 1Neuronal Ceroid-LipofuscinosesAutophagymedicineAnimalsHumansEnzyme Replacement TherapyeducationMolecular BiologyMice Knockouttherapyeducation.field_of_studyTripeptidyl-Peptidase 1030102 biochemistry & molecular biologybiologyAutophagy; cathepsin D; enzyme replacement therapy; lysosome; neuronal ceroid lipofuscinosis; proteolysis; storage; therapyBrainCell BiologyFibroblastsTripeptidyl peptidase Imedicine.diseaseLRP1Cell biologyDisease Models Animal030104 developmental biologylysosomebiology.proteinAllograft inflammatory factor 1Neuronal ceroid lipofuscinosisneuronal ceroid lipofuscinosisLysosomesResearch PaperAutophagy
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Enzyme replacement therapy with recombinant pro-CTSD (cathepsin D) corrects defective proteolysis and autophagy in neuronal ceroid lipofuscinosis

2019

CTSD (cathepsin D) is one of the major lysosomal proteases indispensable for the maintenance of cellular proteostasis by turning over substrates of endocytosis, phagocytosis and autophagy. Consequently, CTSD deficiency leads to a strong impairment of the lysosomal-autophagy machinery. In mice and humans CTSD dysfunction underlies the congenital variant (CLN10) of neuronal ceroid lipofuscinosis (NCL). NCLs are distinct lysosomal storage disorders (LSDs) sharing various hallmarks, namely accumulation of protein aggregates and ceroid lipofuscin leading to neurodegeneration and blindness. The most established and clinically approved approach to treat LSDs is enzyme replacement therapy (ERT) aim…

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