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 55 records · Page 3Linked to original sources
PubMed1980

Status of enzyme replacement therapy for Gaucher disease.

At this point in time, enzyme replacement therapy for Gaucher disease appears both biochemically effective (patients 1-3, and 10) as well as clinically promising (patients 4 and 5), although these salutary responses have not been obtained consistently (patients 6-9). The discrepancy may be due to the method employed for the isolation of the enzyme. One current opinion is that glucocerebrosidase prepared by conventional fractionation and ion exchange chromatographic procedures may have been more effective in vivo than enzyme prepared by butanol extraction and hydrophobic column chromatography, which we developed because of the difficulty in obtaining large quantities of glucocerebrosidase by the conventional method. It should be remembered that the enzyme prepared by the latter procedure was fully active on glucocerebroside in liver biopsy specimens in vitro. Furthermore, glucocerebrosidase prepared by the second method exerted a positive effect in 2 young patients, who received relatively large amounts of enzyme, and in an adult who was treated with corticosteroid prior to infusion of the enzyme. At this moment, a possible explanation is that a necessary associated factor, perhaps a lipid, may have been removed by the large-scale isolation procedure. We are attempting to improve the biochemical and clinical responses to enzyme infusion by investigating the effects of lysosomal modifying agents and by enhancing the uptake and localization of the infused enzyme in lysosomes of cells that contain the stored glucocerebroside.

Clinical Trials as Topic↗
PubMed1987

Does oral enzyme replacement therapy reverse intestinal lactose malabsorption?

The effects of oral enzyme replacement therapy on breath hydrogen excretion and symptoms after milk ingestion were studied in lactase-deficient patients. Sixteen symptomatic patients underwent interval hydrogen breath tests using whole milk as substrate. Each study was repeated with the addition of 250 mg of beta-D-galactosidase derived from Aspergillus oryzae (Lactrase) given orally with the milk. Subsequently seven of those 11 patients who did not normalize their hydrogen excretion with 250 mg of Lactrase were available to be restudied with a 500-mg dose. Mean cumulative and peak hydrogen excretions were calculated for the baseline (milk alone), 250 mg, and 500 mg Lactrase groups. Significant (p less than or equal to 0.05) decreases in cumulative and peak hydrogen excretion were noted between the 500 mg Lactrase versus the baseline group, but not between the 250 mg versus baseline group. Five of the 16 (31%) symptomatic lactase-deficient patients normalized their hydrogen excretion after 250 mg of Lactrase; four of seven (57%) who had not normalized on 250 mg, normalized their hydrogen excretion with 500 mg of Lactrase. A different pattern was observed in the incidence of symptoms. Five of the nine patients (56%) whose hydrogen excretion normalized with the addition of Lactrase at either dosage became asymptomatic after milk ingestion; in addition, three patients who did not normalize their hydrogen also became asymptomatic. We conclude that oral Lactrase in sufficient dosage temporarily reverses lactose malabsorption in some patients.

Adolescent↗
PubMed2002

Repeat abdominal ultrasound evaluation of 100 patients with type I Gaucher disease treated with enzyme replacement therapy for up to 7 years.

With the advent of enzyme replacement therapy for Gaucher disease, there was a need to assess response to treatment repeatedly over relatively short periods of time; hence abdominal ultrasound was used in our referral clinic because it was convenient, safe and inexpensive. In 100 treated patients monitored for 2-7 years, nearly all had reduction in hepatosplenomegaly. The per cent reduction was more dramatic in patients who started treatment when older than 16 years. This effect may be explained by a correlation between per cent reduction and degree of baseline organomegaly. Because children often initiate therapy sufficiently early to preclude developing massive organomegaly, the observed per cent reduction is commensurately less. For all patients treated for more than five years, plateau-ing in response was seen after the first three years of treatment. This study permits us to reconsider less frequent evaluations of organ volumes. Our findings also underscore the efficacy of enzyme replacement, but raise the question of the need for dose reduction as nearly normal organ volumes are achieved.

Abdomen↗
PubMed1982

Infantile hypophosphatasia: enzyme replacement therapy by intravenous infusion of alkaline phosphatase-rich plasma from patients with Paget bone disease.

Enzyme replacement therapy for a severely affected 6-month-old girl with hypophosphatasia was attempted by repeated intravenous infusions of alkaline phosphatase-rich plasma, obtained by plasmapheresis, from two men with Paget bone disease. Circulating Paget AP activity was found to have a half-life (two days) similar to that reported in adults, which did not change during a five-week period of six AP infusions. Normalization of the patient's serum AP activity was followed by better control of her hypercalcemia and hypercalciuria. Sequential radiographic studies revealed arrest of worsening rickets with slight remineralization of metaphyses, although urinary excretion of the AP substrates phosphoethanolamine and inorganic pyrophosphate was unaltered by therapy. Our findings suggest that the infantile form of hypophosphatasia results from defective production of AP rather than from accelerated destruction of circulating enzyme, and that hydrolysis of AP substrates like PEA and PPi occurs primarily in tissue rather than blood. Study of additional cases of hypophosphatasia will be necessary to assess the clinical efficacy of this form of enzyme replacement therapy.

Alkaline Phosphatase↗
PubMed2003

Significance of immune response to enzyme-replacement therapy for patients with a lysosomal storage disorder.

Lysosomal storage disorders are collectively important because they cause significant morbidity and mortality. Patients can present with severe symptoms that include somatic tissue and bone pathology, developmental delay and neurological impairment. Enzyme-replacement therapy has been developed as a treatment strategy for patients with a lysosomal storage disorder, and for many of these disorders this treatment is either in clinical trial or clinical practice. One major complication arising from enzyme infusion into patients with a lysosomal storage disorder is an immune response to the replacement protein. From clinical trials, it is clear that there is considerable variability in the level of immune response to enzyme-replacement therapy, dependent upon the replacement protein being infused and the individual patient. Hypersensitivity reactions, neutralizing antibodies to the replacement protein and altered enzyme targeting or turnover are potential concerns for patients exhibiting an immune response to enzyme-replacement therapy. The relative occurrence and significance of these issues have been appraised.

Animals↗
PubMed1997

[Enzyme replacement therapy: a new treatment concept in Gaucher disease].

Until recently the treatment of lysosomal storage disorders was entirely supportive. A new enzyme replacement therapy has become available in Gaucher's disease, a lipid storage disorder that is due to a genetic defect of beta-glucocerebrosidase. Intravenous infusions of modified beta-glucocerebrosidase has produced clinical improvement in Gaucher patients, with regression of organomegaly and increase in blood counts. At the Children's Hospital of Mainz 13 patients (6 children and 7 adults) were treated with alglucerase on a high-dosage regimen (60 units per kilogram every two weeks). A decrease in liver and spleen size was observed 4 to 6 months after commencement of therapy. Hemoglobin and the number of platelets increased. In some cases, a reduction of the dosage was possible after a year of enzyme replacement-therapy. A growth spurt was observed in the children. The availability of enzyme replacement therapy is limited by its high cost; however, in the future gene transfer may become the treatment of choice.

Adolescent↗
PubMedDate not supplied

Pancreatic enzymes replacement therapy in chronic pancreatitis: an update.

Chronic pancreatitis is the major cause of exocrine pancreatic insufficiency which should be compensated by pancreatic enzyme replacement therapy. There are now available a great number of pancreatic enzyme preparations, but encapsulated enteric-coated microspheres and minimicrospheres are considered the enzyme treatment of choice. However, full compensation of pancreatic exocrine insufficiency with enzyme replacement therapy cannot be obtained in all patients with chronic pancreatitis.

Chronic Disease↗
PubMed1997

Use of enzyme replacement therapy for Gaucher disease during pregnancy.

OBJECTIVE: To date there has been little published experience with enzyme replacement therapy in pregnant women with symptomatic type I Gaucher disease. STUDY DESIGN: We describe six patients, including three with repeated early pregnancy loss, five of whom successfully carried pregnancies to term; the last pregnancy was terminated because of pulmonary hypertension. RESULTS: All pregnancies were uneventful and five resulted in healthy newborns. CONCLUSION: We concluded that in patients with Gaucher disease of childbearing age,for whom obstetric complications are an important symptom of the disease, pregnancy is not contraindicated (unless there is evidence or suspicion of pulmonary hypertension) and treatment should not be interrupted because the clinical improvement engendered by enzyme replacement therapy is conducive to fewer complications during pregnancy and delivery and post partum.

Abortion, Habitual↗
PubMed1982

Gaucher disease: a century of delineation and research. Enzyme replacement therapy: model and clinical studies.

A number of investigators have attempted to treat Gaucher disease with exogenous glucocerebrosidase. Although at times encouraging biochemical changes and suggestive alterations in organomegaly have been reported, overall, the results of enzyme replacement therapy must be judged to be a failure. In order to understand this lack of success with a promising treatment modality, four aspects of enzyme replacement therapy require examination: 1. The purification of glucocerebrosidase to a form which can hydrolyze glucocerebroside under in vivo conditions; 2. The delivery of the enzyme to cells of the macrophage-monocyte system; 3. The intracellular fate of the administered enzyme; 4. The capacity of the enzyme to effectively contact intracellular glycolipid deposits. A model system for the study of the latter three of these aspects of enzyme replacement therapy has been developed. Monocytes from normal subjects and patients with Gaucher disease were maintained in tissue culture for several months using horse serum-containing culture media. When such cells were "fed" glucocerebrosidase, their enzyme deficiency was corrected for at least 72 hours. Cells from Gaucher disease patients do not spontaneously accumulate glucocerebroside in this system. When loaded with 14C-labeled glucocerebroside, they do not become Gaucher cells but rather manifest a remarkable capacity to catabolize glucocerebroside, so that the labeled fatty acid quickly appears in neutral fats and in phospholipids. Therefore, this model is not yet suitable for study of the effectiveness of enzyme therapy.

Cells, Cultured↗
PubMed2005

Enzyme replacement therapy for Gaucher disease in Australia.

AIM: To study the effectiveness of a specific national programme of enzyme replacement therapy (ERT) for patients with severe forms of Gaucher disease, a disorder of sphingolipid metabolism resulting from an inherited deficiency of the lysosomal enzyme beta-Glucocerebrosidase. METHODS: Prospective analysis of data submitted at entry and every 6 months on therapy. The responses of haemoglobin (Hb) and platelet (plt) concentrations, liver and spleen volumes were assessed. PATIENTS: Forty-eight patients were treated with ERT for a minimum of 6 months. Forty patients had Type 1 disease and eight had Type 3B. The age range was 1-70 years (median 24 years). Duration of therapy at the time of analysis was 6-114 months. RESULTS: Thirty-six per cent of patients started with a normal Hb increasing to 76% after 6 months. The mean improvement in Hb from baseline to the end of study period was 20 g/L, when the Hb was normal in 85% (41 patients). Thirty per cent of patients had a normal plt count at the start of therapy, with a more gradual increase in the count at 6 monthly intervals of 50, 91, 108 and 142% of starting value. Seventy-five per cent of patients had a normal plt count at the end of study. Spleen volumes reduced by a mean of 56% in 33 evaluable patients, and the liver by 27% in 30 of 38 evaluable patients. Eight patients had an increase in liver volume of 28%. CONCLUSION: Enzyme replacement therapy produced a spectrum of beneficial responses in patients with Gaucher disease, but all had some evidence of reversal of haematological complications and/or reduction in visceromegaly. Future analyses will examine the effect of therapy on bone disease, prepubertal growth and quality of life.

Adolescent↗
PubMed2006

Improvement of sympathetic skin responses under enzyme replacement therapy in Fabry disease.

AIM: To report the effect of enzyme replacement therapy (ERT) in sympathetic skin responses (SSR) of patients with Fabry disease. PATIENTS AND METHODS: Seven male patients were included in an open-label protocol using agalsidase-alfa, continued at regular intervals. Five patients completed 24 months of ERT and two of them completed 18 months. Two main measurements were performed at baseline, as well as 1 and 2 years after ERT: (1) a standard neurological examination (NE), with a detailed evaluation of the sensory perception of light touch, pinprick, cold, hot, and vibratory stimuli; (2) the SSR amplitudes. RESULTS: Although there were no significant differences between NE in this time period, all patients reported general improvement in their subjective reports of acroparaesthesia and sweating. Before starting ERT, the SSR amplitudes were either too small (3/7 patients) or absent (4/7 patients): the average (range) amplitude of 122 microV (0 through 492) was statistically smaller than that found in a control group, i.e. 1453.6 microV (619.7-2754) (p<0.0001, t-test). Mean +/- SD SSR amplitude increased to 1088+/- 690 microV in the second year of ERT, reaching the range found in a normal control group (p=0.004). CONCLUSION: ERT improved SSR continuously in Fabry patients in 2 years of observation. Although the mechanism of the SSR improvement is unknown, this response to ERT can be clinically significant if it reflects a normalization in sweating.

Age Factors↗
PubMed2001

Magnetic resonance imaging of bone marrow changes in Gaucher disease during enzyme replacement therapy: first German long-term results.

OBJECTIVE: Since 1991, enzyme replacement therapy (ERT) has been available for patients with Gaucher disease in Germany. The aim of this study was to analyse the MR pattern of bone marrow involvement and response to ERT in Gaucher disease type I. PATIENTS AND DESIGN: Thirty patients with Gaucher disease type I had MRI examinations prior to initiation of ERT with alglucerase/imiglucerase and during follow-up. Median MR follow-up and duration of ERT were 36 months. Coronal T1- and T2-weighted spin-echo images of the lower extremities were obtained to evaluate changes in the appearance of yellow marrow. MR images were categorized as having either a homogeneous (type A) or non-homogeneous patchy (type B) appearance of bone involvement and response to ERT was assessed by two radiologists. RESULTS: Overall, 19 of 30 patients (63%) showed an increased signal intensity on T1- and T2-weighted images after 36 months of ERT, consistent with partial reconversion of fatty marrow during treatment. Focal bone lesions surrounded by a low signal intensity (SI) rim did not respond to ERT, suggesting bone infarcts. Of the 11 patients with bone infarcts (low SI rim lesion), 82% had the non-homogeneous type B pattern (P=0.0021). In 86% of patients with splenectomy, bone infarcts were seen (P<0.05). CONCLUSIONS: MRI using T1- and T2-weighted spin-echo sequences is a valuable, non-invasive method for monitoring bone marrow response in patients receiving ERT. A non-homogeneous patchy signal intensity of bone marrow involvement correlates with the presence of bone infarcts (P=0.0021).

Adult↗
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↗
PubMedDate not supplied

Gaucher disease, enzyme replacement therapy, and the Patient Assistance Program.

Gaucher disease is the most common lysosomal storage disorder characterized by a missing enzyme, glucocerebrosidase. Enzyme replacement therapy has been available in the form of Ceredase (Genzyme Corporation, Cambridge, Massachusetts) (alglucerase injection) since 1991, and in the form Cerezyme (Genzyme Corporation, Cambridge, Massachusetts) (imiglucerase for injection) since 1994. Because of the high cost associated with enzyme replacement therapy, the Genzyme Corporation, manufacturers of Ceredase and Cerezyme, developed the Patient Assistance Program. The program assisted those patients who chose to use it with the facilitation of coverage approvals from their insurance carriers. The program has become a comprehensive case management service made up of nurses and social workers who work with patients on many issues from access to coverage. Case managers also provide support to providers who are transitioning patients to home therapy. Home health agencies can benefit from the information and assistance offered by this program as well as other resources throughout Genzyme and the Gaucher community.

Case Management↗
PubMed2004

Monitoring dose response of enzyme replacement therapy in feline mucopolysaccharidosis type VI by tandem mass spectrometry.

Mucopolysaccharidosis type VI is an inherited disorder of glycosaminoglycan metabolism characterized by organomegaly, corneal clouding, and skeletal dysplasia. Recent developments in the use of tandem mass spectrometry to measure sulfated mono- and disaccharides have enabled us to perform noninvasive, biochemical monitoring during therapy regimes in mucopolysaccharidosis type VI cats in addition to established methods of disease evaluation. In this study, mucopolysaccharidosis type VI animals were given high-dose (20 mg/kg) enzyme replacement therapy for the first month after birth followed by low doses (1 mg/kg) for a further 2 mo and were compared with animals maintained on 1 mg/kg enzyme replacement therapy for 3 mo. A sulfated monosaccharide (N-acetylhexosamine) and a sulfated disaccharide (N-acetylhexosamine-uronic acid) were elevated in MPS VI cat urine and blood. These markers showed a clear discrimination between the treatment groups during the first 4 wk of therapy: values in the high-dose group were close to normal whereas those in the low-dose group were only slightly lower than the untreated mucopolysaccharidosis type VI cats. However, within 2 mo of cessation of the high-dose therapy there was minimal difference in the oligosaccharide levels, with both groups lying between the untreated and unaffected cats. At the completion of the trial, subjective minor improvement was noted in overall physical disease features and also in lysosomal vacuolation in tissues from animals on the initial high-dose enzyme replacement therapy compared to the low-dose therapy animals. Initial high-dose therapy reduced storage load in the animals but had no lasting clinical benefit over continuous low-dose therapy.

Animals↗
PubMed2006

Impact of enzyme replacement therapy on cardiac morphology and function and late enhancement in Fabry's cardiomyopathy.

The present study evaluated the evolution of cardiac morphology, function, and late enhancement as a noninvasive marker of myocardial fibrosis, and their inter-relation during enzyme replacement therapy in patients with Fabry's disease using magnetic resonance imaging and color Doppler myocardial imaging. Late enhancement, which was present in up to 50% of patients, was associated with increased left ventricular mass, the failure of a significant regression of hypertrophy during enzyme replacement therapy, and worse segmental myocardial function. Late enhancement may predict the effect of enzyme replacement therapy on left ventricular mass and cardiac function.

Adult↗
PubMedDate not supplied

Intravenous enzyme replacement therapy: better in home or hospital?

This article evaluates satisfaction with enzyme replacement therapy (ERT) at home and at hospital in adult patients with Fabry and Gaucher diseases. A questionnaire was developed and sent to 34 patients with Fabry disease who were receiving ERT with agalsidase alfa (Replagal) and to 49 patients with type I Gaucher disease who were receiving ERT with glucocerebrosidase (Cerezyme). Of the 45 returned questionnaires, 20 were from patients with Fabry disease and 25 from patients with Gaucher disease. Hospital treatment visits were reported as stressful by 18 patients (40%), whereas only 4 (9%) patients reported that home therapy was stressful. Both groups of patients adjusted well to receiving home-based therapy. Nearly all of the patients with Fabry disease (19 patients, 95%) and Gaucher disease (21 patients, 84%) preferred home-based therapy. Treatment in the home was reported as more comfortable, less stressful, more effective and had less impact on family life. Only 4 (9%) patients chose to continue receiving infusions in hospital. The majority of patients with Fabry disease and Gaucher disease found home-based therapy to be more convenient and less stressful than hospital-based therapy.

Adaptation, Psychological↗
PubMed1987

Enzyme replacement therapy in a patient with hyperargininemia.

In a patient with hyperargininemia, enzyme replacement therapy such as whole blood exchange transfusion or erythrocyte transfusion was performed, and its effect was confirmed in vitro as well as in vivo. The patient has been treated with the restriction of protein intake, oral administration of an essential amino acid mixture, and sodium benzoate or phenylacetic acid. With these treatments, his plasma ammonia levels were controlled. On the other hand, plasma and CSF concentrations of arginine were not so well controlled. With whole blood exchange transfusion and erythrocyte transfusion, plasma arginine concentrations and plasma ammonia levels were controlled. These effects have continued for about 3 months. Furthermore, the effect of exchanged erythrocytes on the blood arginine levels was also confirmed by in vitro experimentation that mixes arginine with erythrocytes in the medium RPMI 1640. Arginine concentration of the medium did not decrease when arginine was mixed with erythrocytes of the patient, but when arginine was mixed with erythrocytes of mother or normal controls, it decreased rapidly. In calculation, 10(7) of erythrocytes of the mother or normal controls was presumed to metabolize 4-5 nmole of arginine per day. From these results, the erythrocyte exchange transfusion is considered to be effective for the control of clinical and biochemical abnormalities in this disorder.

Amino Acid Metabolism, Inborn Errors↗