ABSTRACT
BACKGROUND: Gaucher disease (GD) is caused by a deficiency in the lysosomal enzyme glucocerebrosidase. Enzyme replacement therapy (ERT) is recommended for clinical improvement. METHODS: The efficacy and safety of a new imiglucerase, Abcertin, were assessed in 7 Egyptian patients with treatment-naïve type 1 GD. Each patient was administered a biweekly 60âU/kg dose of Abcertin for 6 months. The primary endpoint was the change in hemoglobin concentration. The secondary endpoints were changes from baseline in platelet counts, spleen and liver volumes, biomarker levels, skeletal parameters, and bone mineral density. RESULTS: The hemoglobin concentration increased by a mean of 1.96â±â0.91âg/dL (range 1.11-2.80âg/dL) or 20.6% (Pâ=â.001). Statistically significant increases in the platelet count and decreases in the spleen volume and biomarker levels were also observed. There were no severe drug-related adverse events. One patient developed anti-imiglucerase antibodies without neutralizing activity. CONCLUSION: Our study results demonstrate the efficacy and safety of Abcertin in patients with type 1 GD. This suggests that Abcertin can be an alternative ERT option for type 1 GD.
Subject(s)
Enzyme Replacement Therapy/methods , Gaucher Disease/drug therapy , Glucosylceramidase/pharmacokinetics , Glucosylceramidase/therapeutic use , Recombinant Proteins/pharmacokinetics , Recombinant Proteins/therapeutic use , Adolescent , Area Under Curve , Biomarkers , Bone Density , Child , Child, Preschool , Egypt , Enzyme Replacement Therapy/adverse effects , Glucosylceramidase/adverse effects , Half-Life , Hemoglobins/drug effects , Humans , Liver/drug effects , Male , Metabolic Clearance Rate , Organ Size , Recombinant Proteins/adverse effects , Spleen/drug effectsABSTRACT
OBJECTIVE: We sought to evaluate the clinical role of pepsin for laryngopharyngeal reflux (LPR) in children with otitis media with effusion (OME). METHODS: Pepsin/pepsinogen and fibrinogen were analyzed in fifty effusion and blood samples of children with OME using enzyme linked immunosorbent assay (ELISA). Ambulatory 24-h dual-probe pH monitoring was additionally performed in 31 children divided into two groups according to response of medical treatment. RESULTS: The effusion levels of pepsin/pepsinogen ranged from 8.5 to 1512 µg/dl and were up to 4-540 times higher than the concentrations found in plasma samples. The effusion levels of fibrinogen ranged from 0.05 to 4.1g/dl. Some effusion samples showed fibrinogen concentrations did not exceed 10 times higher than the concentrations found in plasma samples and others showed lower concentrations. The pH of effusion samples was 7.13 to 8.72. Dual-probe pH monitoring showed that 22/31 (71%) of the studied children had significant acid reflux documented by either the esophageal probe or the pharyngeal probe and all of them had LPR. There is a significant positive correlation between the level of pepsin assayed in the effusions and the number of pharyngeal reflux episodes measured by pH monitoring. CONCLUSIONS: Analysis of pepsin/pepsinogen in effusion samples of children with OME, using ELISA, can be considered as a reliable biochemical marker for assessment of laryngopharyngeal reflux.