Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Enzyme replacement therapy”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources
PubMed1993

Correction of neutrophil chemotaxis defect in patients with Gaucher disease by low-dose enzyme replacement therapy.

We have recently described a chemotactic defect in severely afflicted Gaucher disease patients. Two of the patients were treated with low-dose intravenous enzyme replacement (Ceredase). Marked improvement in their hematological status, organomegaly, and growth was observed. In addition, their chemotactic defect and their tendency towards infections were corrected within 1 year of treatment.

Chemotaxis, Leukocyte↗
PubMed1998

[Gaucher's disease and enzyme replacement therapy].

Gaucher disease is an autosomal recessive genetic disorder characterized by a deficiency in the glucocerebrosidase enzyme. Glucocerebroside then accumulates in macrophages (Gaucher cells), causing anemia, thrombocytopenia, organomegaly and major bone problems. Discovery of the enzyme deficiency by Brady in 1964, and subsequent extraction and partial deglycosylation of the native enzyme led to a treatment. 1,600 people out of 5,000 possible worldwide patients benefit from this drug. The 70 French treated patients (out of an estimated 200) show remarkable improvement.

Gaucher Disease↗
PubMed1995

Apparent lack of response of salmon affected by pancreas disease to pancreatic enzyme replacement therapy.

A trial was conducted to establish whether there would be any benefit in feeding mammalian pancreatic enzymes to farmed salmon clinically affected by pancreas disease. Pancreatic enzymes were incorporated at a rate of 4 kg/tonne of feed and fed at 0.6 to 0.9 per cent bodyweight/day for 41 days to one cage of salmon. The weights, lengths and condition factors were established for the fish before and after the feeding trial and compared with those for an adjacent cage of untreated fish. Histopathology and blood amylase and lipase activities were monitored weekly. No significant increases in weight or condition factor, and no reduction in mortalities were recorded. Histopathology confirmed the presence of pancreas disease throughout the trial and there were concurrent skeletal and cardiac myopathies. Blood amylase activities showed no significant change and were considered to be within normal ranges; blood lipase activity remained undetectable.

Amylases↗
PubMed1982

Feasibility of using an isolated intestinal segment as an artificial organ for enzyme replacement therapy.

Guinea pigs fed an ascorbic acid-deficient diet develop scurvy because of the absence of the enzyme L-gulonolactone oxidase. In theory if this enzyme is provided and its substrate L-gulonolactone is present at adequate concentrations ascorbic acid will be synthesized and the development of scurvy prevented. Using this model we tested whether a viable segment of intestine could be used to contain the administered enzyme and act as an artificial organ for the production of ascorbic acid. A surgical procedure was developed to prepare an externalized pouch of intestine with its circulation left intact. When enzyme is inserted in this intestinal bag it is not toxic and not antigenic in some animals, whereas, enzyme injected intraperitoneally is clearly antigenic. Synthesis of ascorbic acid by this artificial organ could not, however, be detected by elevation of plasma concentrations of the vitamin.

Animals↗
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↗
PubMed1989

Pancreatic enzyme replacement therapy. Importance of gastric acid secretion, H2-antagonists, and enteric coating.

The relative efficacy of three commercial pancreatic enzyme supplements in improving fat absorption was studied using the [14C]triolein breath test in 12 patients with chronic pancreatitis. Two of the supplements were enteric coated. The one nonenteric coated product was studied twice: with and without ranitidine coadministration. Doses complied with the manufacturers recommendations. Baseline studies included pentagastrin-stimulated gastric acids, 72-hr fecal fat excretion, and [14C]triolein absorption while not on supplementation. Acid outputs were variable (BAO: 0.3-4.1 meq/hr; MAO: 3.5-34.6 meq/hr). Three patients had mild steatorrhea (i.e., less than 10 g/day) and the remaining severe fat malabsorption (56.9 +/- 41.5 g/day). Although fat absorption was significantly improved by all three supplements, the nonenteric coated preparation was most effective (P less than 0.001). However, laboratory analysis demonstrated that lipase content was four times greater, ie, 17,000 IU/4 tablets. Pretreatment with ranitidine failed to further improve the absorption in patients given nonenteric supplements but was effective in those found to have high or normal acid outputs (P less than 0.001). Our results suggest that the recommended dosage of enteric coated preparations is insufficient for adult patients with severe chronic pancreatitis. Secondly, the marked variability of acid secretion in such patients possibly accounts for the variability of results obtained by others on the usefulness of coadministration of antacids and H2 antagonists. Routine measurement of gastric acid secretion status may help optimize the choice and form of pancreatic enzyme supplementation.

Adult↗
PubMed1993

Low-dose high-frequency enzyme replacement therapy for very young children with severe Gaucher disease.

Six children with a mean age of 4.6 years (range 2.5-7), suffering from severe Gaucher disease, were treated with low-dose high-frequency intravenous enzyme replacement (Ceredase, Genzyme, U.S.A.) for a period of 10-24 months. Although, in general, these patients were more severely affected than previously reported patients, the results of the treatment were as satisfactory as those obtained by using much higher doses at low frequency. In addition to regression of organomegaly and improvement of haematological abnormalities, we observed two unique clinical responses in three patients: two showed decreased tendency to bacterial infections, associated with improvement in neutrophil chemotaxis, and one patient, with type 3 Gaucher disease, showed some improvement in neurological findings. Several measures were taken to ameliorate the burden of the high-frequency treatment. These included implantation of venous access devices, establishment of a home-treatment programme and the application of effective local anaesthesia. Therefore the low-dose high-frequency protocol appears to be both an effective and feasible alternative to the costly high-dose low-frequency protocols even in very young children.

Child↗
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↗
PubMed2004

Targeting macrophages with baculovirus-produced lysosomal enzymes: implications for enzyme replacement therapy of the glycoprotein storage disorder galactosialidosis.

Lysosomal storage diseases (LSDs) are monogenic disorders of metabolism caused by deficiency of hydrolytic enzymes. In several LSDs, cells of the reticuloendothelial (RE) system are the primary targets of the disease. Exogenous administration of recombinant enzymes overproduced in mammalian cells has proved effective for treating the systemic phenotype in nonneuropathic patients with LSDs. However, for the treatment of diseases with primary involvement of the RE system, the production of the therapeutic enzyme in insect cells could be an alternative and advantageous method because glycoproteins expressed in insect cells carry carbohydrates of the pauci-mannose or core-type. These recombinant enzymes are in principle already poised to be internalized by cells that express mannose receptors, including macrophages. Here, we demonstrate that three baculovirus-expressed enzymes, protective protein/cathepsin A (PPCA), neuraminidase (Neu1), and beta-glucosidase, were readily taken up and restored lysosomal function in enzyme-deficient mouse macrophages. The capacity of recombinant PPCA and Neu1 to clear the lysosomal storage in target cells was assessed in PPCA-/- mice, a model of galactosialidosis. Intravenously injected PPCA-/- mice efficiently internalized the corrective enzymes in resident macrophages of many organs. In addition, treated mice showed overall clearance of lysosomal storage in the most affected systemic organs, kidney, liver, and spleen. Our results suggest that ERT with baculovirus-expressed enzymes might be an effective treatment for nonneuropathic patients with galactosialidosis and possibly for others with LSDs that primarily involve the RE system.

Animals↗
PubMed1994

[Enzyme replacement therapy in type 1 Gaucher's disease].

Gaucher disease is a sphingolipid storage disorder caused by a deficiency of the lysosomal enzyme glucocerebrosidase (GC) and the consequent deposition of glucocerebrosides into the cells of the macrophagic system. Among the three types of clinical disease, type 1 leads to hepatosplenomegaly, hypersplenism and skeletal abnormalities including bone pain, osteopenia and fractures. Two pediatric female patients with moderately severe type 1 Gaucher disease were treated with commercially available GC, mannose terminated to be macrophage-targeted. GC was given by intravenous infusion (30 to 60 units per kilogram of body weight every two weeks) for 8 and 18 months. The hemoglobin concentration increased and the serum acid phosphatase decreased in both patients. In the most affected child, hepatic volume decreased significantly and bony symptoms disappeared. Infusions were uneventful except for an episode of anaphylaxis that subsided rapidly, allowed resumption and did not affect efficacy. These observations are in agreement with the international experience in approximately 800 cases, with good tolerance in all type 1 patients who show objective clinical improvement; patterns of response are variable from patient to patient, independent from previous splenectomy, and dose-dependent; the dose can be tapered after a period of time. Antibodies anti-GC are seen in 13% of the patients, but their presence does not have clinical consequences. The cost of the enzyme makes it crucial to define precise indications, optimal dosing schedules, duration of treatment and cost-benefit ratio.

Adolescent↗
PubMed2002

Enzyme replacement therapy for Fabry disease, an inherited nephropathy.

Fabry disease, an X-linked lysosomal storage disease, results from the deficient activity of the enzyme alpha-galactosidase A (alpha-Gal A) and the progressive accumulation of globotriaosylceramide (GL-3) and related glycosphingolipids. In classically affected males with this inherited nephropathy, early and marked GL-3 deposition in the podocytes leads to proteinuria in childhood or adolescence. With increasing age, GL-3 deposition in renal microvascular endothelial cells, and to a lesser extent in interstitial and mesangial cells, leads to renal insufficiency in the third to fifth decades of life. Recently identified "renal variants" who lack the classical disease manifestations of acroparesthesias, angiokeratoma, hypohidrosis, and characteristic corneal/lenticular opacities also develop renal failure. In contrast, "cardiac variants" who also lack the classical phenotype, develop proteinuria in adulthood, but survive a normal lifespan without developing renal failure. Here, we review the renal involvement and pathology in the classical, renal and cardiac variant phenotypes, and present highlights of the preclinical studies and clinical trials that demonstrated the safety and effectiveness of recombinant alpha-Gal A replacement for this inherited nephropathy.

Adult↗
PubMed1996

Modification of Escherichia coli B glutathione synthetase with polyethylene glycol for clinical application to enzyme replacement therapy for glutathione deficiency.

Glutathione synthetase of Escherichia coli B was modified with polyethylene glycol, and the properties of the resultant modified enzyme were investigated. The thermal stability of the modified enzyme and its resistance against several proteases increased compared with those of the native enzyme. The modified enzyme was injected intravenously via the rat tail vein, and the circulating life of the enzyme in plasma was monitored. The half-life of the native enzyme was 50 min, whereas that of the modified enzyme was approximately 24 h. The systemic anaphylaxis reaction was tested by using rats intravenously injected with the native and modified enzymes. For the native enzyme, strong reactions such as dyspnea and tumble were observed; however, no symptom or only a very weak reaction, such as scratching, was observed with the modified enzyme.

Anaphylaxis↗