A5006764055- Parathyroid Disorders and Treatments
- Bone health and treatments
- Magnesium in Health and Disease
- Vitamin D Research Studies
- Connective tissue disorders research
- Medical Imaging and Pathology Studies
- Genetic Syndromes and Imprinting
- Alkaline Phosphatase Research Studies
- Dermatological and Skeletal Disorders
- Bone health and osteoporosis research
- Digestive system and related health
- Hemoglobinopathies and Related Disorders
- Biomedical Research and Pathophysiology
- Heterotopic Ossification and Related Conditions
- Potassium and Related Disorders
- Folate and B Vitamins Research
- Fibroblast Growth Factor Research
- Vitamin C and Antioxidants Research
- Chronic Myeloid Leukemia Treatments
- Muscle and Compartmental Disorders
- Clinical Nutrition and Gastroenterology
- Diet and metabolism studies
- Bone and Dental Protein Studies
- Metabolism and Genetic Disorders
- Iron Metabolism and Disorders
Yale University
2016-2025
Massachusetts Eye and Ear Infirmary
2021
Harvard University
1983-2019
University of North Carolina at Chapel Hill
2019
Indiana University – Purdue University Indianapolis
2018-2019
Indiana University School of Medicine
2019
Innsbruck Medical University
2019
Universität Innsbruck
2019
Duke University
2019
Pharmacosmos (Denmark)
2019
X-linked hypophosphatemia is characterized by increased secretion of fibroblast growth factor 23 (FGF-23), which leads to and consequently rickets, osteomalacia, skeletal deformities. We investigated burosumab, a monoclonal antibody that targets FGF-23, in patients with hypophosphatemia.
Background. X-linked hypophosphatemia (XLH) is the most common heritable form of rickets and osteomalacia. XLH-associated mutations in phosphate-regulating endopeptidase (PHEX) result elevated serum FGF23, decreased renal phosphate reabsorption, low concentrations (inorganic phosphorus, Pi) 1,25-dihydroxyvitamin D [1,25(OH)2D]. KRN23 a human anti-FGF23 antibody developed as potential treatment for XLH. Here, we have assessed safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD),...
In X-linked hypophosphatemia (XLH), inherited loss-of-function mutations in the PHEX gene cause excess circulating levels of fibroblast growth factor 23 (FGF23), leading to lifelong renal phosphate wasting and hypophosphatemia. Adults with XLH present chronic musculoskeletal pain stiffness, short stature, lower limb deformities, fractures, pseudofractures due osteomalacia, accelerated osteoarthritis, dental abscesses, enthesopathy. Burosumab, a fully human monoclonal antibody, binds inhibits...
Intravenous iron enables rapid correction of iron-deficiency anemia, but certain formulations induce fibroblast growth factor 23-mediated hypophosphatemia.To compare risks hypophosphatemia and effects on biomarkers mineral bone homeostasis intravenous isomaltoside (now known as ferric derisomaltose) vs carboxymaltose.Between October 2017 June 2018, 245 patients aged 18 years older with anemia (hemoglobin level ≤11 g/dL; serum ferritin ≤100 ng/mL) intolerance or unresponsiveness to 1 month...
ABSTRACT Tumor-induced osteomalacia (TIO) is caused by phosphaturic mesenchymal tumors producing fibroblast growth factor 23 (FGF23) and characterized impaired phosphate metabolism, skeletal health, quality of life. UX023T-CL201 an ongoing, open-label, phase 2 study investigating the safety efficacy burosumab, a fully human monoclonal antibody that inhibits FGF23, in adults with TIO or cutaneous hypophosphatemia syndrome (CSHS). Key endpoints were changes serum phosphorus assessed transiliac...
Rickets is seen in association with vitamin D deficiency and several genetic disorders associated abnormal mineral ion homeostasis. Studies receptor (VDR)-null mice have demonstrated that expansion of the late hypertrophic chondrocyte layer, characteristic rickets, secondary to impaired apoptosis these cells. The observation normalization homeostasis VDR-null prevents rachitic changes suggests rickets hypocalcemia, hypophosphatemia, or hyperparathyroidism, rather than VDR action. To...
Abstract To address the natural history of Williams syndrome (WS), we performed multisystem assessments on 20 adults with WS over 30 years age and documented a high frequency problems in multiple organ systems. The most striking consistent findings were: abnormal body habitus; mild–moderate sensorineural hearing loss; cardiovascular disease hypertension; gastrointestinal symptoms including diverticular disease; diabetes glucose tolerance standard oral testing; subclinical hypothyroidism;...
Phosphate homeostasis is central to diverse physiologic processes including energy homeostasis, formation of lipid bilayers, and bone formation. Reduced phosphate levels due excessive renal loss cause hypophosphatemic rickets, a disease characterized by prominent defects; conversely, hyperphosphatemia, major complication failure, accompanied parathyroid hyperplasia, hyperparathyroidism, osteodystrophy. Here, we define syndrome featuring both rickets hyperparathyroidism hyperplasia as well...
Background: Evidence suggests that vitamin D status in adults, as assessed by serum 25-hydroxyvitamin (25-OHD), is positively associated with calcium absorption fraction and inversely PTH. Few comparable pediatric data exist.
In X-linked hypophosphatemia (XLH), elevated fibroblast growth factor 23 (FGF23) decreases the renal tubular maximum reabsorption rate of phosphate/glomerular filtration (TmP/GFR) and serum inorganic phosphorus (Pi), resulting in rickets and/or osteomalacia. The objective was to test hypothesis that monthly KRN23 (anti-FGF23 antibody) would safely improve Pi adults with XLH. Two sequential open-label phase 1/2 studies were done. Six academic medical centers used. Twenty-eight XLH...
ABSTRACT Fibroblast growth factor 23 (FGF23) plays a crucial role in renal phosphate regulation, exemplified by the causal of PHEX and DMP1 mutations X-linked hypophosphatemic rickets autosomal recessive type 1, respectively. Using whole exome sequencing we identified compound heterozygous family with sequence similarity 20, member C (FAM20C) two siblings referred for hypophosphatemia severe dental demineralization disease. FAM20C were not found other undiagnosed probands national Norwegian...
X-Linked hypophosphatemia (XLH) is characterized by renal phosphate wasting, with inappropriately low or normal serum 1,25-dihydroxyvitamin D concentrations causing rickets and osteomalacia. Mutations in PHEX result increased fibroblast growth factor 23 (FGF23) expression, elevating circulating FGF23 concentrations. Treating XLH calcitriol may further increase concentrations, based on vitro vivo models.The aim of the study was to investigate whether current standard therapies...
Circulating fibroblast growth factor (FGF)-23 is variably elevated in individuals with X-linked hypophosphatemia (XLH), and klotho has recently been shown to effect renal phosphate handling, yet limited data are available on circulating FGF23 XLH.
Burosumab, a fully human monoclonal antibody to FGF23, is the only approved treatment for X-linked hypophosphatemia (XLH), rare genetic disorder characterized by renal phosphate wasting and substantial cumulative musculoskeletal morbidity. During an initial 24-week randomized, controlled trial, 134 adults with XLH received burosumab 1 mg/kg (n = 68) or placebo 66) every 4 weeks. After 24 weeks, all subjects open-label until week 48. This report describes efficacy safety of during period....
Treatment of X-linked hypophosphatemia (XLH) with active vitamin D metabolites and phosphate can partially correct skeletal deformities. It is unclear whether therapy influences the occurrence two major long-term morbidities in XLH: enthesopathy dental disease. The objective study was to investigate relationship between treatment disease adult XLH patients. designed as observational cross-sectional. conducted at an academic medical center's hospital research unit. Fifty-two patients aged 18...
Idiopathic infantile hypercalcemia (IIH) is a disorder the genetic etiology and physiological basis of which are not well understood.The objective study was to describe underlying physiology cause in an infant with severe IIH extend these findings into additional cohort children IIH.This inpatient single patient consanguineous parents at academic medical center follow-up specialty clinic cohort.The population one for gene discovery testing 27 patients idiopathic replication...