2021
1-13C-propionate breath testing as a surrogate endpoint to assess efficacy of liver-directed therapies in methylmalonic acidemia (MMA)
Manoli I, Pass A, Harrington E, Sloan J, Gagné J, McCoy S, Bell S, Hattenbach J, Leitner B, Duckworth C, Fletcher L, Cassimatis T, Galarreta C, Thurm A, Snow J, Van Ryzin C, Ferry S, Mew N, Shchelochkov O, Chen K, Venditti C. 1-13C-propionate breath testing as a surrogate endpoint to assess efficacy of liver-directed therapies in methylmalonic acidemia (MMA). Genetics In Medicine 2021, 23: 1522-1533. PMID: 33820958, PMCID: PMC8354855, DOI: 10.1038/s41436-021-01143-8.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid Metabolism, Inborn ErrorsBiomarkersBreath TestsHumansLiverMethylmalonic AcidPropionatesConceptsMethylmalonic acidemiaTransplant recipientsBreath testingSerum methylmalonic acid concentrationsLiver transplant recipientsLiver-directed therapiesBone mineral densityNatural history protocolMethylmalonic acid concentrationsOxidative capacityEnteral bolusRenal functionClinical outcomesCognitive test resultsSerum biomarkersMineral densityClinical studiesTherapeutic effectBreath testHealthy volunteersSurrogate endpointsDisease severityRelated disordersGenomic therapyPatients
2020
Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity
O'Mara A, Johnson J, Linderman J, Brychta R, McGehee S, Fletcher L, Fink Y, Kapuria D, Cassimatis T, Kelsey N, Cero C, Sater Z, Piccinini F, Baskin A, Leitner B, Cai H, Millo C, Dieckmann W, Walter M, Javitt N, Rotman Y, Walter P, Ader M, Bergman R, Herscovitch P, Chen K, Cypess A. Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity. Journal Of Clinical Investigation 2020, 130: 2209-2219. PMID: 31961826, PMCID: PMC7190915, DOI: 10.1172/jci131126.Peer-Reviewed Original ResearchConceptsBAT metabolic activityIntravenous glucose tolerance testGlucose tolerance testΒ3-AR agonistInsulin sensitivityTolerance testMetabolic diseasesObesity-related metabolic diseasesWhite adipose tissue lipolysisBrown adipose tissue thermogenesisOpen-label studyTotal bile acidsHuman brown fatHigher insulin sensitivityAdipose tissue lipolysisAdipose tissue thermogenesisPET/CTΒ3-adrenergic receptor agonistIntramural Research ProgramChronic pharmacological stimulationMetabolic activityMirabegron therapyMirabegron treatmentPrimary endpointSecondary endpoints