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Results for “Enzyme replacement therapy”

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At least 19 recordsLinked to original sources
PubMed1975

Investigations in enzyme replacement therapy in lipid storage diseases.

Enzyme replacement appears to offer much promise as specific therapeutic procedures for patients with Fabry's disease and Gaucher's disease. However, enzyme replacement in patients with Tay-Sachs disease and other heritable metabolic disorders where the central nervous system is affected will require first the development of effective methods for the delivery of exogenous enzymes to the brain; such methods are not yet available.

Adolescent↗
PubMed1976

Enzyme replacement therapy--an experiment of nature in a chimeric mannosidosis calf.

Enzyme replacement therapy was studied in a chimeric mannosidosis calf which had received a natural transplacental transplant of normal lymphocytes from its co-twin. There was considerable reduction in the pathology of certain organs and in the amount of storage oligosaccharides, but the clinical course of this neurologic disease was not significantly altered. It was postulated that if this disease had been purely visceral the transplant would have been relatively effective.

Animals↗
PubMed1977

Enzyme replacement therapy in Gaucher's disease: large-scale purification of glucocerebrosidase suitable for human administration.

Enzyme replacement therapy for the alleviation of Gaucher's disease has been impeded because of the difficulty in preparing large amounts of glucocerebrosidase, the enzyme that is deficient in patients with this disorder. A large-scale procedure for the purification of human placental glucocerebrosidase has been developed. The method uses cholate extraction, ammonium sulfate fractionation, acid precipitation, butanol extraction, and hydrophobic chromatography; the final enzyme preparation has a specific activity of more than 10(6) units/mg of protein with an overall recovery of 30%. In addition, the contamination of enzyme preparations, intended for human infusion, prepared by isolation procedures involving concanavalin A columns has been studied and is reported here.

Female↗
PubMed2026

The Effect of Pancreatic Exocrine Insufficiency and Pancreatic Enzyme Replacement Therapy on Gut Microbiome Composition in Pancreatic Disease: A Prospective Cohort Study.

OBJECTIVES: Increasing evidence demonstrates that pancreatic exocrine insufficiency (PEI) is associated with harmful changes to the gut microbiome. The mainstay of PEI treatment is with pancreatic enzyme replacement therapy (PERT), which has been shown to lead to significant survival benefit in pancreatic disease. The aim of this study was to determine how treatment of PEI with PERT affects gut microbiome composition. METHODS: This is a prospective observational cohort study of patients being treated for pancreatic disease at a single centre. PEI status of patients was assessed at the time of recruitment using published diagnostic criteria. Pre-PERT samples were taken before treatment was started and post-PERT samples were taken after at least 4 weeks of treatment. To profile the gut microbiome composition, shotgun metagenomic sequencing was performed with DNA extracted from stool samples. RESULTS: 25 patients with pancreatic disease were included. The abundance of pathogenic bacteria, such as Viridans group Streptococcus and Campylobacter species, was significantly increased in the gut microbiome of patients with PEI compared to those without PEI. Following PERT treatment, analysis of the gut microbiome of treated patients showed a significant reduction in the abundance of multiple pathogenic species, such as those from Viridans group Streptococci, compared to untreated PEI patients. CONCLUSIONS: Treatment with PERT leads to significant changes in the gut microbiome composition of patients with pancreatic disease. Changes include a significant reduction in potentially pathogenic bacteria and so may contribute to the survival benefits seen with PERT treatment in pancreatic disease.

gut microbiome↗
PubMed1991

Is the fluorescein dilaurate test suitable for monitoring the effectiveness of pancreatic enzyme replacement therapy?

We have employed an oral test of pancreatic digestive function using fluorescein dilaurate (a substrate for pancreatic cholesterol ester hydrolase), administered together with pancreatic enzyme supplements, in order to test the hypothesis that urinary excretion of fluorescein provides a simple method for determining the optimal dose of oral pancreatic enzymes. Commercially available pancreatic enzyme supplements had negligible cholesterol hydrolase activity in vitro, and did not increase the urinary excretion of fluorescein when administered together with fluorescein dilaurate in 16 patients with pancreatic exocrine insufficiency. Inhibition of gastric secretion by ranitidine resulted in a statistically significant increase in urinary fluorescein excretion during the fluorescein dilaurate test. The fluorescein dilaurate test is not, therefore, suitable for determining the effectiveness of oral pancreatic enzyme replacement therapy. Moreover, the manufacturer's advice to stop oral pancreatic enzyme therapy for 5 days before performing the fluorescein dilaurate test appears unnecessary, since oral pancreatic enzymes do not alter test results.

Amylases↗
PubMed1976

Enzyme replacement therapy for adenosine deaminase deficiency and severe combined immunodeficiency.

To evaluate their role as a form of replacement therapy, frozen irradiated red blood cells were administered to a child with adenosine deaminase deficiency associated with severe combined immunodeficiency disease. In vitro lymphocyte responses to mitogens and allogeneic cells were restored. Subsequently, a "thymus shadow" appeared, and immunoglobulin synthesis was demonstrated. Frozen irradiated plasma, which alone had no effect on lymphocytes numbers or responses, promoted lymphocytosis when given with frozen irradiated red blood cells. The patient received the transfusions with or without irradiated plasma at four-week intervals and remained free of infection for 17 months. The patient's lymphocyte adenosine triphosphate levels were elevated before therapy, which consistently reduced them without altering the lymphocyte adenosine deaminase activity. Enzyme replacement therapy may provide a way to treat patients with adenosine deaminase deficiency associated with severe combined immunodeficiency disease who do not have histocompatible bone-marrow donors.

Adenosine Deaminase↗
PubMed1977

Enzyme replacement therapy of exocrine pancreatic insufficiency in man. Relations between in vitro enzyme activities and in vivo potency in commercial pancreatic extracts.

I assayed 16 commercially available pancreatic extracts (representing capsules, tablets and enteric-coated tablets) for enzyme activities and the relation between the in vitro activities and in vivo potency evaluated in man. Lipase activity ranged from 10 to 3600 units per unit, with 11 preparations containing less than 600 units per unit. The preparations with the highest lipase activities were llozyme, 3600, Kuzyme HP, 2330, Festal, 2073, Cotazym, 2014, and Viokase, 1636 units. Lipase activity in vitro correlated with potency in vivo for tablets and capsules, with tablets and capsules being effective in reducing steatorrhea by 56.1 +/- 9 per cent and 48.6 +/- 10 per cent (mean +/- S.E.M.) respectively, P less than 0.001. Enteric-coated tablets were less effective (20 +/- 13 per cent reduction, P greater than 0.02). The longer the gastric pH remained greater than or equal to 4 (r = 0.915, P less than 0.01) and the higher the average duodenal pH (r = 0.966, P less than 0.01), the more marked the reduction in steatorrhea.

Administration, Oral↗
PubMed1977

Enzyme replacement therapy in Gaucher's disease: preliminary clinical trial of a new enzyme preparation.

A patient with far-advanced adult type Gaucher's disease was treated with solubilized, highly purified placental glucocerebrosidase administered after entrapment in human erythrocytes or by direct intravenous injection. In some instances the enzyme-containing erythrocytes were coated with gamma globulin. No toxic side effects were observed after enzyme infusion. There were suggestive, but not conclusive, findings that enzyme infusion may have been beneficial. After therapy, there was a decrease in transfusion requirement, some improvement of liver function, possible decrease in liver size, and relief of subjective symptoms. Erythrocyte and plasma glucocerebroside levels were unchanged during therapy, but there was a possibly significant decrease in leukocyte and platelet levels of the glycolipid. No changes occurred in serum acid phosphatase or angiotensin-converting enzyme activity.

Acid Phosphatase↗
PubMed1979

Enzyme replacement therapy by fibroblast transplantation: long-term biochemical study in three cases of Hunter's syndrome.

We have assessed the effectiveness of transplanted histocompatible fibroblasts as a long-lived source of lysosomal enzymes for replacement therapy in three patients with Hunter's syndrome, over periods ranging from 2.5 to 3.75 yr. The level of Hunter corrective factor excreted by all three patients increased after transplantation, as did the activity of alpha-L-idurono-2-sulfate sulfatase in serum, when measured directly with a radioactive disulfated disaccharide substrate. Sulfatase activity was also raised in leukocyte homogenates from the two patients that we were able to assess. These increases in enzyme activity were accompanied by corresponding increases in catabolism of heparan and dermatan sulfates, as shown by (a) a decrease in sulfate:uronic ratios of urinary oligosaccharides, (b) an increase in iduronic acid monosaccharide, and (c) a normalization of Bio-Gel P-2 gel filtration profiles. Both the increase in enzyme activity and increased catabolism were maintained during the period of study and were not affected by either a gradual decrease or total withdrawal of immunosuppressive therapy.

Child↗
PubMed1976

Enzyme replacement therapy in Gaucher's disease: a rapid, high-yield method for purification of glucocerebrosidase.

Gaucher's disease is caused by a deficiency of the lysosomal enzyme glucocerebrosidase (glucosylceramidase; D-glucosyl-N-acylsphingosine glucohydrolase, EC 3.2.1.45); this disorder has been a leading candidate for enzyme replacement trials. A rapid, high-yield method for purification of glucocerebrosidase has been developed. Detergent extraction of human placenta was followed by salt fractionation, concanavalin A-Sepharose chromatography, organic solvent precipitation, and affinity chromatography on phosphatidylserine-agarose; the total yield is 60% with 6000-fold purification. Purified glucocerebrosidase has been administered intravenously to a volunteer Gaucher's patient on two separate occasions. For the first injection, the enzyme was entrapped in resealed erythrocytes; for the second injection, the enzyme was given without any carrier. The enzyme infusions caused no untoward effects.

Erythrocyte Membrane↗
PubMedDate not supplied

Enzyme replacement therapy in Gaucher's and Fabry's disease.

Glucocerebrosidase and ceramidetrihexoside-alpha-galactosidase were obtained in a high degree of purity from human placental tissue. The enzymes were infused in Gaucher and Fabry patients, respectively. Following the administration of the proteins to supplement the genetically determined deficiencies, there resulted a specific reduction in the accumulated hlycolipids in the circulation and liver. These results indicate that enzyme replacement may provide hope for the clinical treatment of these disorders.

Fabry Disease↗
PubMed1992

Enhanced intracellular stability of dextran-horse radish peroxidase conjugate: an approach to enzyme replacement therapy.

Horse radish peroxidase (HRP), a mannose-containing glycoprotein was covalently modified by conjugation with dextran. The rapid uptake of HRP by the liver is markedly inhibited by mannan. The uptake of dextran-HRP conjugate by the liver, though lower compared to that of the free enzyme, is also partially inhibited by mannan. Liposomes were therefore used as carriers for delivering the free and the modified HRP to the liver. The dextran-HRP conjugate showed greater stability intracellularly as compared to the free enzyme. The enhanced stability of enzymes upon their extensive glycosylation with nondegradable sugar polymers would be of importance in extending the catalytic life of therapeutically active enzymes and thereby improve their therapeutic potential for the treatment of certain enzyme deficiency disorders.

Chromatography, Gel↗