scholarly journals Enzyme replacement therapy in mice lacking arylsulfatase B targets bone-remodeling cells, but not chondrocytes

2020 ◽  
Vol 29 (5) ◽  
pp. 803-816 ◽  
Author(s):  
Gretl Hendrickx ◽  
Tatyana Danyukova ◽  
Anke Baranowsky ◽  
Tim Rolvien ◽  
Alexandra Angermann ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Bone Remodeling ◽  
Cell Types ◽  
Skeletal Growth ◽  
Enzyme Replacement ◽  
Mps Vi ◽  
Arylsulfatase B ◽  
The Impact ◽  
Deficient Mice

Abstract Mucopolysaccharidosis type VI (MPS-VI), caused by mutational inactivation of the glycosaminoglycan-degrading enzyme arylsulfatase B (Arsb), is a lysosomal storage disorder primarily affecting the skeleton. We have previously reported that Arsb-deficient mice display high trabecular bone mass and impaired skeletal growth. In the present study, we treated them by weekly injection of recombinant human ARSB (rhARSB) to analyze the impact of enzyme replacement therapy (ERT) on skeletal growth and bone remodeling. We found that all bone-remodeling abnormalities of Arsb-deficient mice were prevented by ERT, whereas chondrocyte defects were not. Likewise, histologic analysis of the surgically removed femoral head from an ERT-treated MPS-VI patient revealed that only chondrocytes were pathologically affected. Remarkably, a side-by-side comparison with other cell types demonstrated that chondrocytes have substantially reduced capacity to endocytose rhARSB, together with low expression of the mannose receptor. We finally took advantage of Arsb-deficient mice to establish quantification of chondroitin sulfation for treatment monitoring. Our data demonstrate that bone-remodeling cell types are accessible to systemically delivered rhARSB, whereas the uptake into chondrocytes is inefficient.

scholarly journals Early Diagnosis and Results of Enzyme Replacement Therapy in the Patient with Mucopolysaccharidosis Type VI: Clinical Case

2021 ◽  
Author(s):  
Dmitry V. Ivanov ◽  
Anna I. Ostrun ◽  
Vladimir M. Kenis ◽  
Tatiana V. Markova ◽  
Ekaterina Yu. Zakharova
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Clinical Case ◽  
Mucopolysaccharidosis Type ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Mucopolysaccharidosis Type Vi ◽  
Mps Vi ◽  
Arylsulfatase B ◽  
Arsb Gene

Background. Mucopolysaccharidosis type VI (MPS VI, Maroteaux–Lamy syndrome) is rare autosomal-recessive multisystem disease, one of the group of lysosomal storage diseases. The MPS VI pathogenesis is determined by arylsulfatase B enzyme deficiency caused by mutations in the ARSB gene. There are only few published clinical examples of this disease that covers the results of early enzyme replacement therapy (ERT) onset.Clinical case description. The child was suspected to have lysosomal storage disease at the age of 1.5 months, it was based on microscopic analysis of blood smears: Alder abnormality was revealed (granulations and red-violet inclusions in neutrophils, monocytes, lymphocytes cytoplasm). The diagnosis was confirmed at the age of 3 months: increased glycosaminoglycans (GAGs) concentration in the urine, arylsulfatase B activity decrease in dried blood spots, and pathogenic variant c.943C>T (p. R315X) in the ARSB gene in homozygous state were revealed. ERT with galsulfase was started at the age of 7 months. There was decrease in excretion of GAGs in urine to normal level after 9 and 15 months of therapy. Normal growth and body proportions for the patient’s age were determined 3 years after continuous ERT. However, there was progression of multiple dysostosis and joint stiffness, as well as eyes lesion.Conclusion. Early ERT onset cannot completely stop MPS VI progression but it allows to reduce the severity of several symptoms and improves patient’s quality of life.

scholarly journals 169 Update on Enzyme Replacement Therapy (ERT) with Recombinant Human Arylsulfatase B (RHASB) for MPS VI (Maroteaux-Lamy)

2005 ◽  
Vol 58 (2) ◽  
pp. 383-383
Author(s):  
P Harmatz ◽  
R Giugliani ◽  
I Schwartz ◽  
N Guffon ◽  
CSA Miranda ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Enzyme Replacement ◽  
Mps Vi ◽  
Arylsulfatase B ◽  
Human Arylsulfatase

Thrombocytopenia associated with galsulfase treatment

2010 ◽  
Vol 30 (7) ◽  
pp. 768-771 ◽  
Author(s):  
Murat Doğan ◽  
Yasar Cesur ◽  
Erdal Peker ◽  
Ahmet F Oner ◽  
Sekibe Zehra Dogan
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Lysosomal Storage Disorder ◽  
Mucopolysaccharidosis Type ◽  
Lysosomal Storage ◽  
Cultured Fibroblasts ◽  
Enzyme Replacement ◽  
Mucopolysaccharidosis Type Vi ◽  
Mps Vi ◽  
Arylsulfatase B

Mucopolysaccharidosis type VI (MPS VI), or Maroteaux-Lamy syndrome, is a lysosomal storage disorder that results from a deficiency of the enzyme N-acetylgalactosamine-4-sulfatase or arylsulfatase B (ASB). It is a relatively rare disorder, with an estimated incidence of 1 in 248,000 to 1 in 300,000. The diagnosis is made on the basis of findings of elevated urine glycosaminoglycans and a deficiency of ASB activity in leukocytes or cultured fibroblasts. In treatment of MPS VI, enzyme replacement therapy (galsulfase; human recombinant ASB enzyme) became available. Infusions of galsulfase were generally well tolerated. But in some patients, infusion-associated reactions including rash, urticaria, headache, hypotension, nausea, and vomiting were documented and were managed successfully by interrupting or slowing the rate of infusion and/or by the administration of antihistamines, antipyretics, corticosteroids, or oxygen. Here, we report a case with MPS VI who developed thrombocytopenia after third dose of therapy. To the best of our knowledge, this is the first report about thrombocytopenia associated with galsulfase therapy in the literature. Additionally, with this report, we want to share our approach for this case.

The Impact of Pancreatic Resection on Exocrine Homeostasis

2014 ◽  
Vol 80 (7) ◽  
pp. 704-709 ◽  
Author(s):  
Swapnil D. Kachare ◽  
Timothy L. Fitzgerald ◽  
Olga Schuth ◽  
Nasreen A. Vohra ◽  
Emmanuel E. Zervos
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Pancreatic Resection ◽  
Univariate Analysis ◽  
Pancreatic Head ◽  
Exocrine Insufficiency ◽  
Enzyme Replacement ◽  
Increased Risk ◽  
The Impact ◽  
Exocrine Dysfunction

Patients undergoing pancreatic resection are at risk for developing postoperative exocrine dysfunction. We sought to determine the incidence of and clinical factors associated with exocrine dysfunction after pancreatectomy. A retrospective review of a prospective database composed of patients undergoing pancreatic resection between 2004 and 2013 was performed. Logistic regression was used to identify preoperative factors that influenced postoperative exocrine insufficiency. One hundred sixty-one patients with complete follow-up were identified. The mean age was 64.1 ± 12.65 years. The majority were: female (51%), white (66%), tobacco users (61%), nondrinkers (68%), nondiabetic (71%), and without preoperative exocrine dysfunction (96%). Average body mass index was 27.8 ± 6.32 kg/m2. Most underwent a pancreaticoduodenectomy (67.3%) for pancreatic cancer (59.6%). Pancreatic fistula occurred in 6.8 per cent. Seven patients were on enzyme replacement therapy preoperatively. Forty-four patients (27%) had postoperative exocrine dysfunction (five of whom were on enzyme replacement therapy preoperatively). Two of seven (29%) of patients with preoperative exocrine dysfunction had complete resolution of their exocrine dysfunction. On univariate analysis, only the type of operation (Whipple) was significantly associated with exocrine dysfunction ( P = 0.04). On multivariate analysis, both female gender and type of operation were independently associated with postoperative exocrine dysfunction ( P = 0.05). Pancreatic exocrine dysfunction occurred less frequently in this population than what is commonly reported in the literature. Female patients undergoing resection of the pancreatic head have significantly increased risk of exocrine dysfunction.

P0067PREDICTORS OF LONG-TERM OUTCOME IN A SPANISH COHORT OF PATIENTS WITH FABRY DISEASE ON ENZYME REPLACEMENT THERAPY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Marian Goicoechea ◽  
Francisco Gomez-Preciado ◽  
Silvia Benito ◽  
Joan Torras ◽  
Roser Torra ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Fabry Disease ◽  
Replacement Therapy ◽  
Left Ventricular ◽  
Response To Therapy ◽  
Clinical Event ◽  
Enzyme Replacement ◽  
Clinical Events ◽  
The Impact

Abstract Background and Aims Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in Fabry disease patients on ERT. Method Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24-120). Results In 69 patients (42 males, 27 females, mean age 44.6 ±13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242 to 128 mg/g (p = 0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR ≤60 ml/min/1.73 m2 (log Rank 12.423, p=0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p=0.043), being these differences more relevant in females (log Rank 18.514, p<0.001) than males (logRank: 3.442, p=0.064). Lower baseline eGFR was associated with a 3- to 7-fold increase in the risk of clinical events in different Cox models. Conclusion GFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes. For the first time, we show that initiation of ERT in women before renal function deteriorates has a similar or even larger impact as in Fabry males to prevent clinical events.

Changing Patterns of Mortality in Gaucher Disease Prior to and Following the Advent of Enzyme Replacement Therapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3799-3799
Author(s):  
Neal J. Weinreb ◽  
Robert E. Lee
Keyword(s):  
Cardiovascular Disease ◽  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Cause Of Death ◽  
Gaucher Disease ◽  
Age At Death ◽  
Enzyme Replacement ◽  
Number Of Patients ◽  
Changing Patterns ◽  
The Impact

Abstract Enzyme replacement therapy (ERT) with exogenous glucosylceramide β-glucosidase (alglucerase, [Ceredase®] or imiglucerase, [Cerezyme®]) has been shown to improve anemia, thrombocytopenia, hepatosplenomegaly, bone symptoms and quality of life in patients with Gaucher disease. However, the impact of ERT on mortality has not been assessed since the inception of ERT in 1991. Data from the epoch prior to the availability of ERT were obtained from the University of Pittsburgh Gaucher Disease Registry. Data from the time period following the advent of ERT were obtained from the International Collaborative Gaucher Group (ICGG) Gaucher Registry and the Ceredase/Cerezyme pharmacovigilance database (Genzyme Corporation). Age of death was obtained for patients with reported Type 1 (non-neuronopathic) Gaucher disease. Only patients with a known cause of death were included in this analysis. Pre-ERT Era (R.E.L.) Post-ERT Era Number of patients 31 137 Treated with ERT No Yes Mean age at death (years) 53.2 55.6 Range of age at death (years) 3–85 0.2–89 Cause of death due to: n % n % • Gaucher disease 4 12.9% 1 0.7% • Leukemia 3 9.7% 7 5.1% • Lymphoma 1 3.2% 3 2.2% • Myeloma 3 9.7% 1 0.7% • Solid tumor 12 38.7% 17 12.4% • Hemorrhage 1 3.2% 14 10.2% • Thromboembolism 0 0.0% 4 2.9% • Other cardiovascular disease 2 6.5% 26 19.0% • Infectious disease 3 9.7% 6 10.9% • Other causes 2 6.5% 49 35.8% These descriptive data collected prior to the advent of ERT and following approval of ERT in 1991 raise intriguing questions about the changing pattern of mortality in Gaucher disease. Any direct comparison of these populations must be qualified by the possibility of detection bias or a cohort effect. Therefore, pending further information, it is difficult to attribute significance to the difference in mean age at death between the two populations. However, there have been shifts in the pattern of the causes of death. Most notably, deaths due to the primary manifestations of Gaucher disease and to hematologic cancers and solid tumors appear substantially less common in the post-ERT era whereas the proportion of deaths due to cardiovascular disease and other causes appears to be increasing. More accurate estimates of the patterns of mortality in Gaucher disease remain to be determined, particularly for the pre-ERT era. Additional studies of the changing patterns of mortality in Gaucher disease are ongoing.

The impact of enzyme replacement therapy on the progression of Pompe disease

2015 ◽  
Vol 25 ◽  
pp. S189 ◽  
Author(s):  
M. De Antonio ◽  
D. Hamroun ◽  
B. Perniconi ◽  
N. Taouagh ◽  
E. Salort-Campana ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Pompe Disease ◽  
Enzyme Replacement ◽  
The Impact
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