2022
Response of enthesopathy in ENPP1 deficiency to enzyme replacement therapy in murine models and enthesopathy comorbidities and quality of life in ENPP1‐deficient adults
Ansh A, Nester C, O'Brien C, Stabach P, Murtada S, Lester E, Khursigara G, Molloy L, Carpenter T, Ferreira C, Braddock D. Response of enthesopathy in ENPP1 deficiency to enzyme replacement therapy in murine models and enthesopathy comorbidities and quality of life in ENPP1‐deficient adults. The FASEB Journal 2022, 36 DOI: 10.1096/fasebj.2022.36.s1.r5311.Peer-Reviewed Original ResearchENPP1 deficiencyQuality of lifeMusculoskeletal complicationsReplacement therapyBrief Pain Inventory-Short FormPhysical Function Short FormAchilles tendon calcificationHealth-related qualityMajority of patientsCervical spine fusionPresence of enthesopathyAnalgesic medicationRegular chowResidual painAdult patientsDose escalationPhysical functionCardiovascular calcificationTendon calcificationAchilles tendonSpine fusionMurine modelHypophosphatemic ricketsEnzyme replacementPatients
2020
Catalysis‐Independent ENPP1 Protein Signaling Regulates Mammalian Bone Mass
Zimmerman K, Liu X, von Kroge S, Stabach P, Lester ER, Chu EY, Srivastava S, Somerman MJ, Tommasini SM, Busse B, Schinke T, Carpenter TO, Oheim R, Braddock DT. Catalysis‐Independent ENPP1 Protein Signaling Regulates Mammalian Bone Mass. Journal Of Bone And Mineral Research 2020, 37: 1733-1749. PMID: 35773783, PMCID: PMC9709593, DOI: 10.1002/jbmr.4640.Peer-Reviewed Original ResearchConceptsHeterotopic mineralizationBone massFibroblast growth factor 23Growth factor 23Low bone massSoft tissue calcificationEarly-onset osteoporosisFrizzled-related protein 1Soluble Wnt inhibitorsTrabecular bone microarchitectureENPP1 deficiencyΒ-catenin signalingFactor 23Plasma FGF23Vascular calcificationArterial calcificationNuclear β-cateninPlasma PPiBone microarchitectureMurine modelTissue calcificationPlasma PiWnt inhibitorsCalcificationMiceImproving the Pharmacodynamics and In Vivo Activity of ENPP1‐Fc Through Protein and Glycosylation Engineering
Stabach PR, Zimmerman K, Adame A, Kavanagh D, Saeui CT, Agatemor C, Gray S, Cao W, De La Cruz EM, Yarema KJ, Braddock DT. Improving the Pharmacodynamics and In Vivo Activity of ENPP1‐Fc Through Protein and Glycosylation Engineering. Clinical And Translational Science 2020, 14: 362-372. PMID: 33064927, PMCID: PMC7877847, DOI: 10.1111/cts.12887.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArea Under CurveDisease Models, AnimalEnzyme Replacement TherapyGlycosylationHalf-LifeHistocompatibility Antigens Class IHumansMaleMice, TransgenicPhosphoric Diester HydrolasesProtein EngineeringProtein Structure, TertiaryPyrophosphatasesReceptors, FcRecombinant Fusion ProteinsVascular CalcificationConceptsProtein engineeringO-BuN-glycansGlycosylation engineeringCellular recyclingENPP1-deficient miceTerminal sialylationBiomanufacturing platformProtein therapeuticsCalcification disordersSialylationCellsVivo activityFc neonatal receptorTherapeuticsArterial calcificationProteinMurine modelManNAcEnzyme replacementNeonatal receptorEfficacious levelsGeneral strategyThree-prong strategyDrug potency