A5057863019- Lysosomal Storage Disorders Research
- Trypanosoma species research and implications
- Glycogen Storage Diseases and Myoclonus
- Cellular transport and secretion
- Calcium signaling and nucleotide metabolism
- Carbohydrate Chemistry and Synthesis
- Family and Disability Support Research
- Neurogenetic and Muscular Disorders Research
- Biomedical Research and Pathophysiology
- Pineapple and bromelain studies
- Child Nutrition and Feeding Issues
- Studies on Chitinases and Chitosanases
- Cystic Fibrosis Research Advances
- Adenosine and Purinergic Signaling
- Autoimmune and Inflammatory Disorders Research
- Research on Leishmaniasis Studies
- Glycosylation and Glycoproteins Research
- Metabolism and Genetic Disorders
- Biochemical and Molecular Research
- Renal Diseases and Glomerulopathies
- Blood disorders and treatments
- Protease and Inhibitor Mechanisms
- Bone Metabolism and Diseases
- Oral and gingival health research
- Fetal and Pediatric Neurological Disorders
University Medical Center Hamburg-Eppendorf
2016-2025
Universität Hamburg
2016-2025
Klinik und Poliklinik für Kinder- und Jugendmedizin
2003-2024
Universitätskinderklinik
2019
University Medical Center
2017-2019
Heidelberg University
2017
University Hospital Heidelberg
2017
German Cancer Research Center
2017
Eppendorf (Germany)
2016
Pediatrics and Genetics
2016
Current therapies for Fabry disease are based on reversing intracellular accumulation of globotriaosylceramide (Gb3) by enzyme replacement therapy (ERT) or chaperone-mediated stabilization the defective enzyme, thereby alleviating lysosomal dysfunction. However, their effect in reversal end-organ damage, like kidney injury and chronic disease, remains unclear. In this study, ultrastructural analysis serial human biopsies showed that long-term use ERT reduced Gb3 podocytes but did not reverse...
Mucopolysaccharidosis types IIIA through IIID (Sanfilippo syndrome) are caused by deficiencies of enzymes involved in the degradation heparan sulfate. The onset and severity disease highly variable. purpose this study was to describe natural course mucopolysaccharidosis type a large cohort patients.The assessed 71 patients using detailed questionnaire 4-point scoring system compared with 14 IIIB 4 IIIC.In IIIA, first symptoms were observed, on average, at 7 months age. Speech motor...
Fabry's disease (FD) is an X-linked lysosomal storage disorder caused by the deficient activity of enzyme α-galactosidase A (α-Gal A) leading to intracellular accumulation globotriaosylceramide (Gb3). Patients with amenable mutations can be treated migalastat, a recently approved oral pharmacologic chaperone increase endogenous α-Gal activity. We assessed safety along cardiovascular, renal, and patient-reported outcomes biomarkers in prospective observational multicenter study after 12...
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme α-galactosidase A (GLA/AGAL) resulting in accumulation globotriaosylceramide (Gb3). Patients with amenable GLA mutations can be treated migalastat, oral pharmacologic chaperone increasing endogenous AGAL activity. In this prospective observational multicenter study safety as well cardiovascular, renal, and patient-reported outcomes biomarkers were assessed after 12 24 months migalastat treatment...
Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for young Hurler patients. Despite halting neurocognitive decline and improvement life expectancy, beneficial effect on skeletal system limited. As orthopedic complications are one most disabling factors following HSCT, this points to need new strategies. The study summarizes musculoskeletal manifestations in 19 transplanted patients.Data were obtained retrospectively. Patients' charts physical examinations joint range...
Enzyme replacement therapy (ERT) has been shown to improve outcome in classical infantile Pompe disease. The purpose of this study was assess mortality, morbidity, and shortcomings ERT a larger cohort patients treated outside clinical trials. To accomplish this, we retrospectively analyzed the data all 23 subjects with disease having started Germany between January 2003 December 2010.Ten (43%) deceased four others (17%) became ventilator dependent. Seven infants (30.5%) made no motor...
To evaluate functional and morphometric magnetic resonance neurography of the dorsal root ganglion peripheral nerve segments in patients with Fabry painful neuropathy.In this prospective study, lumbosacral ganglia proximal lower extremity were examined 11 male disease by a standardized 3T protocol. Volumes L3 to S2 ganglia, perfusion parameters L5-S1 spinal L5, cross-sectional area sciatic compared healthy controls.Dorsal symmetrically enlarged 78% (L3), 94% (L4), 122% (L5), 115% (S1), 119%...
Abstract Introduction Long‐term outcome data provide important insights into the clinical utility of enzyme replacement therapies. Such are presented for velmanase alfa in treatment alpha‐mannosidosis (AM). Methods Patient ( n = 33; 14 adults, 19 paediatric) from development programme were integrated this prospectively‐designed analysis long‐term efficacy and safety. Patients who participated phase I/II or III trials continuing to receive after completion invited participate a comprehensive...
Mutations in the GNPTAB and GNPTG genes cause mucolipidosis (ML) type II, III alpha/beta, gamma, which are autosomal recessively inherited lysosomal storage disorders. encode α/β-precursor γ-subunit of N-acetylglucosamine (GlcNAc)-1-phosphotransferase, respectively, key enzyme for generation mannose 6-phosphate targeting signals on enzymes. Defective GlcNAc-1-phosphotransferase results missorting enzymes accumulation non-degradable macromolecules lysosomes, strongly impairing cellular...
Alpha-mannosidosis (AM) is a rare, autosomal recessive, lysosomal storage disorder caused by alpha-mannosidase deficiency that leads to the accumulation of mannose-rich oligosaccharides. AM symptoms and severity vary among individuals; consequently, often not diagnosed until late childhood. Velmanase alfa (VA), recombinant human product, first enzyme replacement therapy indicated treat non-neurological in Europe. Previous studies suggested early VA treatment children may produce greater...
Sanfilippo syndrome type A (mucopolysaccharidosis IIIA) is a lysosomal disorder wherein deficient heparan-N-sulfatase (HNS) activity results in the accumulation of heparan sulfate central nervous system and associated with progressive neurodegeneration early childhood. We report on efficacy, pharmacokinetics, safety, tolerability intrathecal (IT) administration recombinant human HNS (rhHNS) from phase IIb randomized open-label trial. Twenty-one patients, 1:1:1 to rhHNS IT 45 mg administered...
Introduction Fabry's disease is an X-linked lysosomal storage disorder caused by reduced activity of α-galactosidase A (GAL), leading to premature death on account renal, cardiac, and vascular organ failure. Accumulation the GAL substrate globotriaosylceramide (Gb3) in endothelial smooth muscle cells associated with early cell damage, suggesting dysfunction as a driver cardiorenal Here, we studied expression key angiogenic factors, VEGFα its antagonist angiostatin, Fabry α-GAL-Tg/KO mice...
The aim of our multicenter study was to investigate the safety and efficacy enzyme replacement therapy (ERT) chaperone on disease progression in female Fabry (FD) patients compare individual treatment regimens. Data from 3 consecutive visits 102 FD 6 centers were retrospectively analyzed. According their FD-specific treatment, separated 5 groups: Newly agalsidase-beta- [n = 18], agalsidase-alfa- 29] migalastat-[n 14] treated patients, long-term 7] agalsidase-alfa-[n 34] patients. Clinical...
The primary treatment outcomes of a phase 2, randomized, double‐blind, pilot study evaluating safety, physiological, and pharmacological effects elosulfase alfa in patients with Morquio A syndrome are herewith presented. Patients aged ≥7 years able to walk ≥200 m the 6‐min test (6MWT) were randomized 2.0 or 4.0 mg/kg/week for 27 weeks. objective was evaluate safety both doses. Secondary objectives on endurance (6MWT 3‐min stair climb [3MSCT]), exercise capacity (cardio‐pulmonary [CPET]),...
Neurological dysfunction represents a significant clinical component of many the mucopolysaccharidoses (also known as MPS disorders). The accurate and consistent assessment neuropsychological function is essential to gain greater understanding precise natural history these conditions design effective trials evaluate impact therapies on brain. In 2017, an International Consensus Panel published recommendations for best practice in conduct studies investigating effects cognitive adaptive...