2025
Modeling bone marrow microenvironment and hematopoietic dysregulation in Gaucher disease through VavCre mediated Gba deletion
Belinsky G, Ruan J, Fattahi N, Mehta S, Boddupalli C, Mistry P, Nair S. Modeling bone marrow microenvironment and hematopoietic dysregulation in Gaucher disease through VavCre mediated Gba deletion. Human Molecular Genetics 2025, ddaf045. PMID: 40197748, DOI: 10.1093/hmg/ddaf045.Peer-Reviewed Original ResearchGD miceImmune dysregulationGaucher diseaseExpansion of monocytesImmune cell deconvolutionKnockout modelsBone marrow microenvironmentGlucocerebrosidase activityC57BL/6 J backgroundDeficient glucocerebrosidase activityGaucher cell infiltrationInfluence disease severityGD biomarkersGD pathologyGD pathophysiologyLysosomal storage disorderImmune landscapeDendritic cellsHematopoietic stemMarrow microenvironmentAccumulation of glucosylceramideVav-CreBone marrowCell infiltrationHematopoietic cellsChallenges in Gaucher disease: Perspectives from an expert panel
Grabowski G, Kishnani P, Alcalay R, Prakalapakorn S, Rosenbloom B, Tuason D, Weinreb N. Challenges in Gaucher disease: Perspectives from an expert panel. Molecular Genetics And Metabolism 2025, 145: 109074. PMID: 40112481, DOI: 10.1016/j.ymgme.2025.109074.Peer-Reviewed Original ResearchGD type 1Enzyme replacement therapyNeuronopathic diseaseGD type 2Type 1Central nervous systemMagnetic resonance imagingGaucher diseaseDixon quantitative chemical shift imagingFirst-line treatment of adultsEnzyme replacement therapy productsDual-energy X-ray absorptiometry scanPrompt initiation of treatmentEffects of enzyme replacement therapyX-ray absorptiometry scanQuantitative chemical shift imagingSymptoms of central nervous systemGD type 1 patientsGD type 3Non-Hodgkin's lymphomaPeak bone massFirst-line treatmentType 2Nervous systemInitiation of treatmentEliglustat substrate reduction therapy in children with Gaucher disease type 1
Ain N, Saith A, Ruan A, Yang R, Burton A, Mistry P. Eliglustat substrate reduction therapy in children with Gaucher disease type 1. Frontiers In Pediatrics 2025, 13: 1543136. PMID: 40083427, PMCID: PMC11903696, DOI: 10.3389/fped.2025.1543136.Peer-Reviewed Original ResearchEnzyme replacement therapySubstrate reduction therapyGD1 patientsPediatric patientsReduction therapyOral substrate reduction therapyPrimary outcomeAlternative to enzyme replacement therapyIntravenous enzyme replacement therapyLevels compared to baselineGaucher disease type 1Indicator of disease activityParent-reported qualityCYP2D6 metabolizer statusRare lysosomal storage disorderProspective case seriesGaucher diseaseType 1 Gaucher diseaseQuality of lifeDisease indicationsLysosomal storage disorderPROMIS questionnairesReplacement therapyCase seriesClinical benefit
2024
Intrinsic link between PGRN and Gba1 D409V mutation dosage in potentiating Gaucher disease
Lin Y, Zhao X, Liou B, Fannin V, Zhang W, Setchell K, Wang X, Pan D, Grabowski G, Liu C, Sun Y. Intrinsic link between PGRN and Gba1 D409V mutation dosage in potentiating Gaucher disease. Human Molecular Genetics 2024, 33: 1771-1788. PMID: 39101473, PMCID: PMC11458007, DOI: 10.1093/hmg/ddae113.Peer-Reviewed Original ResearchGaucher diseaseMutation dosageMouse modelDisease severityProgrammed cell deathRetinal gliosisBrain transcriptomic analysisGD pathogenesisPGRN deficiencyTissue fibrosisDisease progressionGrn-/- miceSevere phenotypeGlycosphingolipid accumulationTranscriptome analysisInflammatory responseGCase functionMiceCell deathShort life spanNeurobehavioral analysisDiseaseGCase activityNeurodegenerative diseasesPGRNPlain language summary of a study looking at the long-term benefits of enzyme replacement therapy in children and teenagers with Gaucher disease type 3
El-Beshlawy A, Tylki-Szymanska A, Belmatoug N, Mistry P. Plain language summary of a study looking at the long-term benefits of enzyme replacement therapy in children and teenagers with Gaucher disease type 3. Future Rare Diseases 2024, 4: frd52. DOI: 10.2217/frd-2023-0015.Peer-Reviewed Original ResearchBeta-glucosidase enzymePlain Language SummaryGaucher diseaseSlow growthBeta-glucosidaseEnzyme replacement therapyLanguage SummaryQuality of life of peopleLife-prolonging treatmentInternational Collaborative Gaucher GroupQuality of lifeGenetic conditionsEnzymeType 3Year of treatmentImproved most symptomsLong-term symptoms
2023
Osteonecrosis in Gaucher disease in the era of multiple therapies: Biomarker set for risk stratification from a tertiary referral center
Basiri M, Ghaffari M, Ruan J, Murugesan V, Kleytman N, Belinsky G, Akhavan A, Lischuk A, Guo L, Klinger K, Mistry P. Osteonecrosis in Gaucher disease in the era of multiple therapies: Biomarker set for risk stratification from a tertiary referral center. ELife 2023, 12: e87537. PMID: 37249220, PMCID: PMC10317498, DOI: 10.7554/elife.87537.Peer-Reviewed Original ResearchConceptsEnzyme replacement therapySubstrate reduction therapyAvascular osteonecrosisTertiary referral centerGaucher diseaseReferral centerTreatment initiationGD patientsImiglucerase enzyme replacement therapyResidual disease activityAnti-drug antibodiesYears of treatmentType of therapyRare inborn errorMixed-effects logistic modelGD1 patientsSpleen statusDisease activityClinical outcomesRisk stratificationReplacement therapyIndependent correlatesMultiple therapiesReduction therapyHigh riskP310: Project Searchlight study methodology: Real-world evaluation and validation of an algorithm to identify persons at risk of Gaucher disease
King L, Aguiar M, Chiorean A, Dumitriu A, Hull J, Mistry P, Modave F, Montmerle M, Pavlick P, Shah N, Weinreb N, Wilson A. P310: Project Searchlight study methodology: Real-world evaluation and validation of an algorithm to identify persons at risk of Gaucher disease. Genetics In Medicine Open 2023, 1: 100338. DOI: 10.1016/j.gimo.2023.100338.Peer-Reviewed Original Research
2022
PGRN deficiency exacerbates, whereas a brain penetrant PGRN derivative protects, GBA1 mutation-associated pathologies and diseases
Zhao X, Lin Y, Liou B, Fu W, Jian J, Fannin V, Zhang W, Setchell K, Grabowski G, Sun Y, Liu C. PGRN deficiency exacerbates, whereas a brain penetrant PGRN derivative protects, GBA1 mutation-associated pathologies and diseases. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 120: e2210442120. PMID: 36574647, PMCID: PMC9910439, DOI: 10.1073/pnas.2210442120.Peer-Reviewed Original ResearchConceptsBlood-brain barrierParkinson's diseaseGaucher diseasePGRN deficiencyPD-like phenotypesRelevant mouse modelRare lysosomal storage diseaseCommon neurodegenerative disorderVisceral symptomsNeurobehavioral deficitsSevere neuroinflammationPD pathologyLysosomal storage diseaseTherapeutic studiesMouse modelNeuronopathic involvementProgranulinImpaired autophagyNeurodegenerative disordersGD phenotypeEarly onsetMiceDiseaseFirst linePathologyCancer risk and gammopathies in 2123 adults with Gaucher disease type 1 in the International Gaucher Group Gaucher Registry
Rosenbloom BE, Cappellini MD, Weinreb NJ, Dragosky M, Revel‐Vilk S, Batista JL, Sekulic D, Mistry PK. Cancer risk and gammopathies in 2123 adults with Gaucher disease type 1 in the International Gaucher Group Gaucher Registry. American Journal Of Hematology 2022, 97: 1337-1347. PMID: 36054609, PMCID: PMC9541044, DOI: 10.1002/ajh.26675.Peer-Reviewed Original ResearchConceptsGD type 1Multiple myelomaGaucher RegistryHematological malignanciesCancer riskGeneral populationSmall single-center studiesType 1Gaucher diseaseAge-specific incidence ratesGaucher disease type 1End Results (SEER) databaseSingle-center studyDiagnosis of MGUSInternational observational studyNon-Hodgkin lymphomaCare of patientsLung cancer riskTypes of malignanciesGeneral US populationDisease type 1Precise risk estimatesUnited States populationGD1 patientsCumulative incidenceNeuroinflammation in neuronopathic Gaucher disease: Role of microglia and NK cells, biomarkers, and response to substrate reduction therapy
Boddupalli CS, Nair S, Belinsky G, Gans J, Teeple E, Nguyen TH, Mehta S, Guo L, Kramer ML, Ruan J, Wang H, Davison M, Kumar D, Vidyadhara D, Zhang B, Klinger K, Mistry PK. Neuroinflammation in neuronopathic Gaucher disease: Role of microglia and NK cells, biomarkers, and response to substrate reduction therapy. ELife 2022, 11: e79830. PMID: 35972072, PMCID: PMC9381039, DOI: 10.7554/elife.79830.Peer-Reviewed Original ResearchConceptsNeuronopathic Gaucher diseaseAmelioration of neuroinflammationNK cellsGaucher diseaseSerum neurofilament light chainInvolvement of microgliaActivation of microgliaRole of microgliaProminent pathological featureNeurofilament light chainBlood-derived macrophagesRare neurodegenerative disorderGlucosylceramide synthaseNeuroinflammation pathwaysSerum NFMicroglia activationNeuronal injuryImmune infiltratesImproved survivalBrain macrophagesPathological featuresGD patientsClinical trialsMacrophage compartmentPatient managementNeuronal activity induces glucosylceramide that is secreted via exosomes for lysosomal degradation in glia
Wang L, Lin G, Zuo Z, Li Y, Byeon S, Pandey A, Bellen H. Neuronal activity induces glucosylceramide that is secreted via exosomes for lysosomal degradation in glia. Science Advances 2022, 8: eabn3326. PMID: 35857503, PMCID: PMC9278864, DOI: 10.1126/sciadv.abn3326.Peer-Reviewed Original ResearchTransjugular Intrahepatic Portosystemic Shunt for Refractory Ascites in Gaucher Disease
Adhyaru K, Menezes S, Mistry PK, Nagral A, Mistry P. Transjugular Intrahepatic Portosystemic Shunt for Refractory Ascites in Gaucher Disease. Cureus 2022, 14: e23941. PMID: 35535294, PMCID: PMC9079779, DOI: 10.7759/cureus.23941.Peer-Reviewed Original ResearchHepatic venous pressure gradientGaucher diseaseRefractory ascitesTransjugular intrahepatic portosystemic shuntTransjugular intrahepatic portosystemic shunt (TIPS) procedureAdvanced hepatic diseaseVenous pressure gradientIntrahepatic portosystemic shuntAnterior abdominal wallPortosystemic shunt procedureEnzyme replacement therapyAvascular osteonecrosisLiver transplantationLysosomal storage disorderPortal hypertensionVariceal bleedingSevere cytopeniaHepatic encephalopathyVenous collateralsLiver diseaseShunt procedurePortosystemic shuntReplacement therapyHepatic diseaseAbdominal wallOverlapping and divergent hepatic and lipoprotein phenotypes in untreated adults with acid sphingomyelinase deficiency versus untreated adults with Gaucher disease from two pivotal clinical trials
Cassiman D, Mistry P, Jones S, Lachmann R, Lukina E, Prada C, Thurberg B, Wasserstein M, Foster M, Patel R, Ribes M, Underhill L, Peterschmitt M. Overlapping and divergent hepatic and lipoprotein phenotypes in untreated adults with acid sphingomyelinase deficiency versus untreated adults with Gaucher disease from two pivotal clinical trials. Molecular Genetics And Metabolism 2022, 135: s29. DOI: 10.1016/j.ymgme.2021.11.058.Peer-Reviewed Original ResearchProject Searchlight Gaucher study design: Real-world evaluation and validation of a rare disease algorithm to identify persons at risk of Gaucher disease using data from electronic health records in the United States
King L, Aguiar M, Chiorean A, Dumitriu A, Mistry P, Modave F, Montmerle M, Pavlick P, Weinreb N, Wilson A. Project Searchlight Gaucher study design: Real-world evaluation and validation of a rare disease algorithm to identify persons at risk of Gaucher disease using data from electronic health records in the United States. Molecular Genetics And Metabolism 2022, 135: s114. DOI: 10.1016/j.ymgme.2021.11.303.Peer-Reviewed Original ResearchPhenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders
Napolioni V, Fredericks CA, Kim Y, Channappa D, Khan RR, Kim LH, Zafar F, Couthouis J, Davidzon GA, Mormino EC, Gitler AD, Montine TJ, Schüle B, Greicius MD. Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders. Biomedicines 2022, 10: 160. PMID: 35052839, PMCID: PMC8774039, DOI: 10.3390/biomedicines10010160.Peer-Reviewed Original ResearchLewy body spectrum disordersParkinson's diseaseDisease patientsPathogenic roleGlucocerebrosidase 1 (GBA1) geneLewy body dementiaEarly disease onsetSystematic literature searchGaucher disease patientsPhenotypic heterogeneityNeuropathologic evaluationNeuropathologic featuresPathological featuresDisease onsetClinical penetranceSpectrum disorderGBA p.Index caseGaucher diseaseLiterature searchUnaffected relativesPatientsDiseaseNonsense variantAffected subjects
2021
Long-read single molecule real-time (SMRT) sequencing of GBA1 locus in Gaucher disease national cohort from Argentina reveals high frequency of complex allele underlying severe skeletal phenotypes: Collaborative study from the Argentine Group for Diagnosis and Treatment of Gaucher Disease
Drelichman G, Escobar N, Soberon B, Basack N, Frabasil J, Schenone A, Aguilar G, Larroudé M, Knight J, Zhao D, Ruan J, Mistry PK, Disease A. Long-read single molecule real-time (SMRT) sequencing of GBA1 locus in Gaucher disease national cohort from Argentina reveals high frequency of complex allele underlying severe skeletal phenotypes: Collaborative study from the Argentine Group for Diagnosis and Treatment of Gaucher Disease. Molecular Genetics And Metabolism Reports 2021, 29: 100820. PMID: 34820281, PMCID: PMC8600149, DOI: 10.1016/j.ymgmr.2021.100820.Peer-Reviewed Original ResearchSevere skeletal manifestationsDiagnóstico y tratamientoSevere skeletal phenotypeGenotype/phenotype correlationGrupo ArgentinoNational cohortDisease manifestationsSkeletal manifestationsGaucher diseaseSkeletal diseaseLarge burdenDiseaseSkeletal phenotypePhenotype correlationComplex allelesArgentine groupCollaborative studyManifestationsChildhoodCollaborative groupsGroupHigh frequencyCohortIncremental biomarker and clinical outcomes after switch from enzyme therapy to eliglustat substrate reduction therapy in Gaucher disease
Kleytman N, Ruan J, Ruan A, Zhang B, Murugesan V, Lin H, Guo L, Klinger K, Mistry PK. Incremental biomarker and clinical outcomes after switch from enzyme therapy to eliglustat substrate reduction therapy in Gaucher disease. Molecular Genetics And Metabolism Reports 2021, 29: 100798. PMID: 34485083, PMCID: PMC8408524, DOI: 10.1016/j.ymgmr.2021.100798.Peer-Reviewed Original ResearchLong-term enzyme replacement therapyEnzyme replacement therapySubstrate reduction therapyGaucher diseaseStable patientsReduction therapySingle tertiary referral centerPhase 3 clinical trialsChronic metabolic inflammationFirst-line therapyTertiary referral centerGD type 1Primary metabolic defectLipid-laden cellsType 1 patientsGD type 1 patientsSubstrate glucosylceramideDisease activityOral therapyReferral centerAvascular necrosisMetabolic inflammationWeek infusionClinical outcomesInflammatory cascadeProgranulin associates with Rab2 and is involved in autophagosome-lysosome fusion in Gaucher disease
Zhao X, Liberti R, Jian J, Fu W, Hettinghouse A, Sun Y, Liu C. Progranulin associates with Rab2 and is involved in autophagosome-lysosome fusion in Gaucher disease. Journal Of Molecular Medicine 2021, 99: 1639-1654. PMID: 34453183, PMCID: PMC8541919, DOI: 10.1007/s00109-021-02127-6.Peer-Reviewed Original ResearchConceptsLysosomal storage diseaseGaucher diseaseAutophagosome-lysosome fusionCommon lysosomal storage diseasePGRN deficiencyNovel therapiesAnimal modelsProgranulinLC3-IIMolecular targetsCrucial mediatorCritical moleculesStorage diseaseDiseaseAutophagic fluxC-terminal fragmentImpaired fusionPatient fibroblastsAutophagyImpairmentKey regulatorThe clinical spectrum of SARS-CoV-2 infection in Gaucher disease: Effect of both a pandemic and a rare disease that disrupts the immune system
Narayanan P, Nair S, Balwani M, Malinis M, Mistry P. The clinical spectrum of SARS-CoV-2 infection in Gaucher disease: Effect of both a pandemic and a rare disease that disrupts the immune system. Molecular Genetics And Metabolism 2021, 135: 115-121. PMID: 34412940, PMCID: PMC8361210, DOI: 10.1016/j.ymgme.2021.08.004.Peer-Reviewed Case Reports and Technical NotesConceptsSARS-CoV-2 infectionType 1 Gaucher diseaseSARS-CoV-2Gaucher diseaseRare diseaseCOVID-19Immune system dysfunctionRare disease populationMedian agePediatric patientsCase seriesFemale patientsAdverse outcomesClinical spectrumIntensive careGD patientsSystem dysfunctionRetrospective analysisDisease populationHigh riskGeneral populationPatientsImmune systemDiseaseSimilar frequencyMiglustat Therapy for SCARB2-Associated Action Myoclonus–Renal Failure Syndrome
Quraishi IH, Szekely AM, Shirali AC, Mistry PK, Hirsch LJ. Miglustat Therapy for SCARB2-Associated Action Myoclonus–Renal Failure Syndrome. Neurology Genetics 2021, 7: e614. PMID: 34337151, PMCID: PMC8320328, DOI: 10.1212/nxg.0000000000000614.Peer-Reviewed Original ResearchAction myoclonus-renal failure syndromeNeurologic symptomsAction myoclonusFailure syndromeProgressive myoclonic epilepsySubstrate reduction therapyWhole-exome sequencingMiglustat therapyAvailable medicationsEarly mortalityReduction therapyMyoclonic epilepsySteady worseningGaucher diseaseMyoclonusGlycosphingolipid metabolismExome sequencingGene mutationsGlucosylceramide accumulationPatientsSeizuresMiglustatSyndromeTherapySymptoms
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