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Pancreatic enzyme therapy and nutritional status of outpatients with chronic pancreatitis.

Patients with chronic pancreatitis are at risk for poor nutritional status. The two major clinical features of chronic pancreatitis are abdominal pain and maldigestion, both resulting in malnutrition. Abdominal pain often results in decreased oral intake, and decreased enzyme production results in maldigestion. Enzyme therapy often is included in treating chronic pancreatitis. There is limited data on the nutritional assessment of outpatients with chronic pancreatitis, and the efficacy of the use of enzyme therapy remains controversial. Serum albumin level and measurement of ideal body weight …

[Gaucher's disease with D409H/D409H genotype. evolution with enzyme replacement therapy].

Gaucher's disease is caused by mutations in the gene encoding glucocerebrosidase. The D409H mutation is the third most frequent mutation in Spain and has been associated with a particular phenotype, including oculomotor apraxia and cardiac valvular calcifications in late childhood. We report a 4-year-old patient, homozygous for the D409H mutation, who was diagnosed with Gaucher's disease at the age of 45days. Enzyme replacement therapy was started at the age of 2months. We report the patient's evolution after 4years of treatment.

Enzyme replacement therapy in a feline model of Maroteaux-Lamy syndrome.

We report studies that suggest enzyme replacement therapy will result in a significant reduction in disease progression and tissue pathology in patients with Maroteaux-Lamy syndrome (Mucopolysaccharidosis type VI, MPS VI). A feline model for MPS VI was used to evaluate tissue distribution and clinical efficacy of three forms of recombinant human N-acetylgalactosamine-4-sulfatase (rh4S, EC 3.1.6.1). Intravenously administered rh4S was rapidly cleared from circulation. The majority of rh4S was distributed to liver, but was also detected in most other tissues. Tissue half-life was approximately 2

Symptomatic effect of pancreatic enzyme therapy in patients with chronic pancreatitis.

The symptomatic effect of pancreatic enzyme substitution therapy was examined in a 4-week double-blind crossover study. Twenty patients, 11 with and 9 without steatorrhoea, were examined. Pancreatic steatorrhoea was reduced from a median of 24 g/day to 10 g/day by the enzyme therapy (P less than 0.01). No significant pain reduction was found in either of the two groups, although there was a tendency to reduction in pain and analgetic consumption in the patients with steatorrhoea when treated with pancreatic enzymes. It is concluded that pancreatic steatorrhoea is still the only indication for …

Systems analyses of the Fabry kidney transcriptome and its response to enzyme replacement therapy identified and cross-validated enzyme replacement therapy-resistant targets amenable to drug repurposing.

Fabry disease is a rare disorder caused by variations in the alpha-galactosidase gene. To a degree, Fabry disease is manageable via enzyme replacement therapy (ERT). By understanding the molecular basis of Fabry nephropathy (FN) and ERT's long-term impact, here we aimed to provide a framework for selection of potential disease biomarkers and drug targets. We obtained biopsies from eight control individuals and two independent FN cohorts comprising 16 individuals taken prior to and after up to ten years of ERT, and performed RNAseq analysis. Combining pathway-centered analyses with network-scie

Metabolic enzyme-based cancer therapy: Mechanisms, delivery strategies, and translational challenges.

Cancer remains one of the leading causes of global mortality, underscoring the need for therapeutic strategies that are both effective and selective. Enzyme-based cancer therapy has emerged as a promising approach by exploiting tumor-specific metabolic dependencies, redox vulnerabilities, and nutrient auxotrophy. This review critically examines recent advances in anticancer enzyme therapy, focusing on amino acid-degrading and redox-modulating enzymes, their mechanisms of action, and translational potential. We integrate insights across enzyme classes to highlight shared therapeutic principles,…

Lactate-sensitive nanomachines for enzyme-controlled drug delivery in cancer therapy.

Here, we report the preparation of a novel enzyme-powered nanomachine for a drug delivery system based on mesoporous silica nanoparticles capped with a cyclodextrin-lactate oxidase (CD-LOx) complex, which enables controlled cargo release triggered by the presence of L-lactate in the tumor microenvironment. To this end, mesoporous silica nanoparticles were functionalized with diphenylethane-1,2-dione moieties and subsequently loaded with a cargo molecule. In parallel, a CD-LOx complex was prepared to act as a capping agent through supramolecular interactions, enabling controlled release of the

Advances in Pompe Disease Treatment: From Enzyme Replacement to Gene Therapy.

Pompe disease is a neuromuscular disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), hydrolyzing glycogen to glucose. Pathological glycogen storage, the hallmark of the disease, disrupts the metabolism and function of various cell types, especially muscle cells, leading to cardiac, motor, and respiratory dysfunctions. The spectrum of Pompe disease manifestations spans two main forms: classical infantile-onset (IOPD) and late-onset (LOPD). IOPD, caused by almost complete GAA deficiency, presents at birth and leads to premature death by the age of 2 years withou

Enzyme replacement therapy improves erythropoiesis and iron dysregulation in Gaucher disease.

Anemia and hyperferritinemia are frequent findings at diagnosis of Gaucher disease (GD). Macrophage-independent dyserythropoiesis and abnormal iron metabolism have been shown. We evaluated hematological and iron status at diagnosis (T0) and the effect of enzyme replacement therapy (ERT) on erythropoiesis and iron utilization over 5-year follow-up in type 1 GD patients and in an ex vivo model of erythropoiesis from CD34 + peripheral blood cells. At T0, 41% of patients had anemia and 51% hyperferritinemia. Hemoglobin increased from 12.6 (T0) to 13.9 g/dL (T6), GFD15, a marker of ineffective eryt

Correction of oxidative stress enhances enzyme replacement therapy in Pompe disease.

Pompe disease is a metabolic myopathy due to acid alpha-glucosidase deficiency. In addition to glycogen storage, secondary dysregulation of cellular functions, such as autophagy and oxidative stress, contributes to the disease pathophysiology. We have tested whether oxidative stress impacts on enzyme replacement therapy with recombinant human alpha-glucosidase (rhGAA), currently the standard of care for Pompe disease patients, and whether correction of oxidative stress may be beneficial for rhGAA therapy. We found elevated oxidative stress levels in tissues from the Pompe disease murine model

[Enzyme replacement therapy in adult patients with type I Gaucher disease].

Enzyme replacement therapy (ERT) is the standard for the treatment of Gaucher disease (GD). A lifelong intravenous administration of a recombinant analogue of human glucocerebrosidase compensates for the functional deficiency of its own enzyme. The use of ERT has changed the clinical phenotype of GD, a severe progressive disease has been turned into the status of an asymptomatic metabolic defect. At the same time, a reduced dosing ERT regimen applied in Gaucher patients who had achieved therapeutic goals has not yet been developed.

Enzyme replacement therapy and white matter hyperintensity progression in Fabry disease.

OBJECTIVE: To explore the association between enzyme replacement therapy (ERT), clinical characteristics, and the rate of progression of white matter hyperintensities (WMH) in patients with Fabry disease (FD). METHODS: Patients with a confirmed diagnosis of FD, aged 18 years or older, participating in an existing FD observational study (NCT00196742), with at least 2 serial MRI brain scans at least 2 years apart for the period between December 2006 and August 2016 were included in this cohort study. Total WMH volume was estimated for each image using a semiautomated procedure. We performed lin

Long-Term Effects of Enzyme Replacement Therapy for Anderson-Fabry Disease.

Anderson-Fabry disease is a rare X-linked lysosomal storage disease caused by α-galactosidase A (α-GalA) gene variants and characterized by a large genotypic and phenotypic spectrum. Enzyme replacement therapy (ERT) using recombinant α-GalA has been approved for > 10 years as a specific therapy for the disease. However, the long-term clinical efficacy for cardiac manifestations has been equivocal because it depends on several factors such as genotype, sex, age, and disease severity at the initiation of ERT. We report the differences in the clinical effects of ERT continued for > 10 years in th

Neuroimaging findings in infantile Pompe patients treated with enzyme replacement therapy.

BACKGROUND: Recombinant human acid α-glucosidase (rhGAA) enzyme replacement therapy (ERT) has prolonged survival in infantile Pompe disease (IPD), but has unmasked central nervous system (CNS) changes. METHODS: Brain imaging, consisting of computed tomography (CT) and/or magnetic resonance imaging (MRI), was performed on 23 patients with IPD (17 CRIM-positive, 6 CRIM-negative) aged 2-38months. Most patients had baseline neuroimaging performed prior to the initiation of ERT. Follow-up neuroimaging was performed in eight. RESULTS: Sixteen patients (70%) had neuroimaging abnormalities consistin

Intrathecal enzyme replacement therapy reverses cognitive decline in mucopolysaccharidosis type I.

Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disease that seriously affects the brain. Severity of neurocognitive symptoms in attenuated MPS subtype (MPS IA) broadly varies partially, due to restricted permeability of blood-brain barrier (BBB) which limits treatment effects of intravenously applied α-L-iduronidase (rhIDU) enzyme. Intrathecal (IT) rhIDU application as a possible solution to circumvent BBB improved brain outcomes in canine models; therefore, our study quantifies effects of IT rhIDU on brain structure and function in an MPS IA patient with previous progr

New therapeutic approaches for Pompe disease: enzyme replacement therapy and beyond.

Pompe disease is an autosomal recessive disorder of glycogen metabolism caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). Prior to 2006, therapy was palliative. Severely affected infants with Pompe succumbed to cardiomyopathy or respiratory failure by one year of age. Enzyme replacement therapy (ERT) with alglucosidase alfa (Genzyme, Cambridge, MA, USA) is currently the only approved treatment for Pompe disease which has improved overall survival, ventilator-free survival, cardiomyopathy, and motor development in infants. In patients with late onset Pompe disease, ER

Cost-effectiveness of enzyme replacement therapy for type 1 Gaucher disease.

ObjectiveTo evaluate the cost-effectiveness of enzyme replacement therapy (ERT) compared to standard medical care without ERT in the Dutch cohort of patients with type 1 Gaucher disease (GD I).DesignCost-effectiveness analysis was performed using a life-time state-transition model of the disease's natural course. Transition probabilities, effectiveness data and costs were derived from retrospective data and prospective follow-up of the Dutch study cohort.SettingThe tertiary referral center for Gaucher disease in the Netherlands.ParticipantsThe Dutch cohort of patients with GD I.InterventionERT

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… Although imiglucerase is not authorized within the EU as an orphan drug, simply because the European orphan drug act was installed at a later stage, the questions with regard to long term outcome of this enzyme therapy and cost-effectiveness are not different compared to other orphan diseases, such as … Without the possibility for complex modeling, a comparison was made of cost-effectiveness of enzyme therapy versus no specific treatment for patients with GD I and a comparison of different dosage regimens. …

Hunter syndrome follow-up after 1 year of enzyme-replacement therapy.

Mucopolysaccharidosis II (Hunter syndrome) is a rare x-linked disorder caused by a deficiency in the lysosomal enzyme iduronate-2-sulphatase, leading to an accumulation of the glycosaminoglycans (GAGs) dermatansulphate and heparan sulphate. The consequence of GAGs accumulation is progressive, multiorgan disease. Enzyme-replacement therapy is hypothesised to result in disease stabilisation and improved prognosis. We present a severe case of Hunter syndrome diagnosed at age 2 years and 4 months, who started enzyme-replacement therapy at the age of 3 years and 3 months. We report his evolution af