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 risk
2021
Incremental 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 cascadeMiglustat 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 accumulationPatientsSeizuresMiglustatSyndromeTherapySymptomsClinical outcomes after 4.5 years of eliglustat therapy for Gaucher disease type 1: Phase 3 ENGAGE trial final results
Mistry PK, Lukina E, Turkia H, Shankar SP, Feldman H, Ghosn M, Mehta A, Packman S, Lau H, Petakov M, Assouline S, Balwani M, Danda S, Hadjiev E, Ortega A, Foster MC, Gaemers SJM, Peterschmitt MJ. Clinical outcomes after 4.5 years of eliglustat therapy for Gaucher disease type 1: Phase 3 ENGAGE trial final results. American Journal Of Hematology 2021, 96: 1156-1165. PMID: 34161616, PMCID: PMC8457136, DOI: 10.1002/ajh.26276.Peer-Reviewed Original ResearchConceptsDisease type 1Gaucher disease type 1Type 1Disease manifestationsENGAGE trialOpen-label extension periodOral substrate reduction therapySpine T-scoreYears of treatmentSubstrate reduction therapyMagnitude of improvementEliglustat therapyMean hemoglobinUntreated patientsAdverse eventsTrial cohortClinical outcomesEligible adultsPlatelet countUntreated adultsSpleen volumeLiver volumeHematologic parametersReduction therapyPatients
2019
Two years of efficacy of oral eliglustat in treatment-naïve and switch patients enrolled in the International Collaborative Gaucher Group Gaucher registry
Mistry P, Balwani M, Charrow J, Kishnani P, Niederau C, McClain M. Two years of efficacy of oral eliglustat in treatment-naïve and switch patients enrolled in the International Collaborative Gaucher Group Gaucher registry. Molecular Genetics And Metabolism 2019, 126: s100-s101. DOI: 10.1016/j.ymgme.2018.12.252.Peer-Reviewed Original ResearchX109/LTreatment-naïve patientsInternational Collaborative Gaucher Group Gaucher RegistryGaucher disease type 1Enzyme replacement therapySwitch patientsMean hemoglobinPlatelet countLiver volumeGaucher RegistrySpleen volumeClinical trialsOral substrate reduction therapyLong-term clinical improvementCYP2D6 metabolizer phenotypeMajor disease manifestationsDisease type 1Substrate reduction therapyKey disease parametersOral eliglustatTreatment-naïveClinical improvementChitotriosidase levelsDisease manifestationsReduction therapy
2015
Recommendations for the use of eliglustat in the treatment of adults with Gaucher disease type 1 in the United States
Balwani M, Burrow TA, Charrow J, Goker-Alpan O, Kaplan P, Kishnani PS, Mistry P, Ruskin J, Weinreb N. Recommendations for the use of eliglustat in the treatment of adults with Gaucher disease type 1 in the United States. Molecular Genetics And Metabolism 2015, 117: 95-103. PMID: 26387627, DOI: 10.1016/j.ymgme.2015.09.002.Peer-Reviewed Original ResearchConceptsGaucher disease type 1Disease type 1Type 1Oral substrate reduction therapyGaucher diseaseFirst-line therapyFirst-line treatmentTreatment of adultsCare of patientsEnzyme replacement therapyMonitoring of patientsPanel of physiciansSubstrate reduction therapyEliglustat therapyReplacement therapyMultisystem diseaseClinical trialsReduction therapyBone marrowTherapySkeletal diseaseEliglustatLysosomes of cellsDeficient activityDisease
2013
Engage: A Phase 3, Randomized, Double-blind, Placebo-controlled, Multi-center Study To Investigate The Efficacy and Safety Of Eliglustat In Adults With Gaucher Disease Type 1: 9 Month Results
Shankar S, Lukina E, Amato D, Dasouki M, Packman S, Pastores G, Assouline S, Balwani M, Mistry P, Ross L, Marulkar S, Peterschmitt M. Engage: A Phase 3, Randomized, Double-blind, Placebo-controlled, Multi-center Study To Investigate The Efficacy and Safety Of Eliglustat In Adults With Gaucher Disease Type 1: 9 Month Results. Blood 2013, 122: 2275. DOI: 10.1182/blood.v122.21.2275.2275.Peer-Reviewed Original ResearchGaucher disease type 1Disease type 1Spleen volumeSubstrate reduction therapyType 1Efficacy endpointUntreated adultsLiver volumeReduction therapyBone marrowDisease severity scoring systemOral substrate reduction therapyBone mineral density changesAdvisory CommitteePrimary efficacy endpointSecondary efficacy endpointsSymptomatic bone diseaseMainstay of therapyOpen-label trialPhase 3 trialBone marrow burden scoreMineral density changesBurden of diseaseCommon lysosomal storage disorderSeverity scoring system