Enzyme Replacement Therapy In Patients Research Articles

667P Glycogen response to enzyme replacement therapy in patients with Pompe disease

667P Glycogen response to enzyme replacement therapy in patients with Pompe disease

Intracerebroventricular Enzyme Replacement Therapy in Patients with Neuropathic Form of Mucopolysaccharidosis Type II: to Help Practicing Physician

Mucopolysaccharidosis type II (Hunter syndrome, MPS II) is a rare hereditary disease from the group of hereditary metabolic diseases. There are neuropathic and non-neuropathic forms of this disease. The neuropathic form is most common and leads to severe cognitive impairment and progressive damage of central nervous system. Nowadays, early diagnosis and timely initiation of pathogenetic therapy in patients with orphan diseases is the crucial problem of modern pediatrics. Intracerebroventricular administration of idursulfase beta is one of the promising treatment options in patients with neuropathic form of MPS II as it prevents severe complications development. The study of new pathogenetic therapy methods for rare hereditary diseases will help doctors of pediatric specialties to route patient correctly in timely manner to receive all the necessary treatment.

Experts' Opinion in Fabry Disease Management and the Unmet Medical Need: The Saudi Perspective.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by α-galactosidase A gene mutations. Its global incidence ranges from 1:40,000 to 1:170,000. This expert review evaluates the available guidelines, the status of diagnosed but untreated patients with FD, and the challenges in diagnosing and managing FD in the Kingdom of Saudi Arabia (KSA). An advisory board meeting (ABM) was conducted in two phases, with a survey that aimed to receive insights on the current unmet needs in the management of patients with FD in November 2022, and a second, offline meeting in February 2023. The goal of this ABM was to discuss current unmet needs in the management of Fabry patients in the Kingdom of Saudi Arabia. In the first ABM, experts opined on the best practices in the diagnosis, screening, and management of FD for healthcare professionals. These opinions on the management of FD relied on data from research and expert clinical judgments. In the second ABM, the same panel discussed different aspects of FD diagnosis, treatment, and management in the member countries of the Gulf Cooperation Council. The experts discussed the stigma associated with FD, patient awareness and knowledge, genetic screening, biomarkers, and home infusion therapy. They reviewed international guidelines and clinical criteria for enzyme replacement therapy (ERT). Furthermore, they also discussed the diagnosis of FD in men and women, the current guidelines followed for monitoring patients with FD, monitoring untreated patients with FD, Fabry Stabilization IndeX (FASTEX) as an assessment tool for the diagnosis of FD, FD management in KSA, challenges encountered while prescribing ERT in patients with FD, and the clinical criteria for starting ERT. The discussions led to the conclusion that currently, ERT is the only available therapy to manage FD and research should be focused on the early diagnosis and management of FD.

Long-term cardiovascular outcomes and mortality with enzyme replacement therapy in patients with mucopolysaccharidosis type II.

Mucopolysaccharidosis type II (MPS II) is a rare multisystemic lysosomal disorder in which cardiac issues can lead to serious dysfunction and an increased risk of fatal cardiac failure. However, studies on major adverse cardiac event (MACE) outcomes in MPS II are lacking. This study evaluated the cardiovascular outcomes and impact of enzyme replacement therapy (ERT) in patients with MPS II in South Korea. In this national cohort study, utilizing data from the National Health Insurance Database, we evaluated 127 patients with MPS II over a 14-year period to investigate the effects of ERT on MACE and all-cause mortality. We tracked MACE incidence, defined by hospitalizations for cardiovascular events, from diagnosis and adjusted the hazard ratios for MACE using Cox modeling. Over an average follow-up period of 7.3 years, we identified 16 cases of MACE among patients (17.35 per 1000 person-years; 95% confidence interval, 10.74-26.83). Patients receiving ERT exhibited a significantly lower incidence of MACE than untreated patients, with cumulative incidences showing a marked difference of 8.3 years. Notably, initiating ERT at earlier stages post-diagnosis was associated with improved outcomes, underscoring the importance of timely treatment. The key risk factors for MACE included specific arrhythmias, a history of invasive procedures, and depression. Early ERT significantly reduced MACE risk and increased survival in patients with MPS II. This underscores the importance of prompt treatment initiation and comprehensive care to address key risk factors and advocates for an expanded therapeutic strategy to enhance MPS II outcomes.

A Feasibility Open-Labeled Clinical Trial Using a Second-Generation Artificial-Intelligence-Based Therapeutic Regimen in Patients with Gaucher Disease Treated with Enzyme Replacement Therapy.

Background/Objectives: Gaucher Disease type 1 (GD1) is a recessively inherited lysosomal storage disorder caused by a deficiency in the enzyme β-glucocerebrosidase. Enzyme replacement therapy (ERT) has become the standard of care for patients with GD. However, over 10% of patients experience an incomplete response or partial loss of response to ERT, necessitating the exploration of alternative approaches to enhance treatment outcomes. The present feasibility study aimed to determine the feasibility of using a second-generation artificial intelligence (AI) system that introduces variability into dosing regimens for ERT to improve the response to treatment and potentially overcome the partial loss of response to the enzyme. Methods: This was an open-label, prospective, single-center proof-of-concept study. Five patients with GD1 who received ERT were enrolled. The study used the Altus Care™ cellular-phone-based application, which incorporated an algorithm-based approach to offer random dosing regimens within a pre-defined range set by the physician. The app enabled personalized therapeutic regimens with variations in dosages and administration times. Results: The second-generation AI-based personalized regimen was associated with stable responses to ERT in patients with GD1. The SF-36 quality of life scores improved in one patient, and the sense of change in health improved in two; platelet levels increased in two patients, and hemoglobin remained stable. The system demonstrated a high engagement rate among patients and caregivers, showing compliance with the treatment regimen. Conclusions: This feasibility study highlights the potential of using variability-based regimens to enhance ERT effectiveness in GD and calls for further and longer trials to validate these findings.

#2401 Association of clinical characteristics with relative changes in plasma lyso-Gb3 levels by enzyme replacement therapy in patients with Fabry disease

Abstract Background and Aims Enzyme replacement therapy (ERT) is an established treatment for Fabry disease (FD), notably for its efficacy in reducing plasma globotriaosylceramide (Gb3) levels. FD is characterized by the accumulation of Gb3 in lysosomes, resulting in the formation of globotriaosylsphingosine (lyso-Gb3), a degradation product associated with disease severity. While numerous studies have demonstrated that ERT can reduce plasma lyso-Gb3 levels, these reductions are usually quantified in absolute terms. This study is the first to explore the relative changes in plasma lyso-Gb3 levels due to ERT and to investigate the association of these changes with patients' clinical characteristics through a retrospective analysis. Method This study included patients with FD who attended the division of Nephrology at our hospital. We excluded patients lacking sufficient clinical data or without plasma lyso-Gb3 measurements both before and after initiating ERT. We considered pre-ERT plasma lyso-Gb3 concentrations as the baseline and evaluated the relative changes at one year post-ERT and at the lowest recorded lyso-Gb3 level after ERT. These variations were compared across various clinical backgrounds to assess their correlation with clinical factors including age, gender, type of ERT medication (agalsidase α or β), and disease severity, as determined by the FASTEX score. Results This study included twelve patients with FD (5 males, 7 females). We observed significantly greater relative declining changes in plasma lyso-Gb3 concentration among males compared to females (one year: −71.9 ± 4.5% in males vs. −20.6 ± 13.7% in females, p < 0.01; minimum levels: −78.5 ± 8.9% in males vs. −48.4 ± 19.6% in females, p = 0.01). No significant difference emerged in lyso-Gb3 reduction between agalsidase α and β treatments over all. One year after treatment, the relative changes in the levels were −45.1 ± 32.6% for agalsidase α and −37.7 ± 24.2% for agalsidase β (p = 0.68). The minimum levels followed suit, with −59.4 ± 26.8% for agalsidase α and −63.2 ± 15.2% for agalsidase β (p = 0.78). Lastly, the relative changes in lyso-Gb3 one year after initiating ERT were significantly associated with age (r = −0.873, p < 0.001), FASTEX score (r = 0.814, p = 0.001), baseline α-galactosidase A activity (r = −0.833, p = 0.001), and baseline lyso-Gb3 levels (r = 0.877, p < 0.001). Additionally, at the lowest levels, the relative changes in lyso-Gb3 showed a significant association with baseline α-galactosidase A activity (r = −0.887, p < 0.001), and baseline lyso-Gb3 levels (r = 0.702, p = 0.011). Conclusion The findings of our study suggest that relative changes in lyso-Gb3 are more pronounced in male patients, those with lower baseline α-galactosidase A activity, and those with higher baseline plasma lyso-Gb3 levels. Patients exhibiting severe α-galactosidase A deficiency and more severe clinical symptoms may experience greater relative declines in plasma lyso-Gb3 concentration following ERT.

Updated Evaluation of Agalsidase Alfa Enzyme Replacement Therapy for Patients with Fabry Disease: Insights from Real-World Data.

The clinical use of agalsidase alfa as enzyme replacement therapy (ERT) for Fabry disease (FD) has spread since 2001, and a large body of evidence of its effectiveness has been collected. This review presents the clinical and laboratory results achieved with agalsidase alfa, which has been published in the literature. Agalsidase alfa infusion slows down or stops the progression of renal damage, expressed by reduction or stabilization of the annual decline of the glomerular filtration rate; yearly decrease of glomerular filtration rate (slope) sometimes is reduced until its stabilization. ERT prevents or reduces the occurrence of hypertrophic cardiomyopathy or slows the increase over time if it is already present. Moreover, regarding neurological manifestations, ERT improves neuropathic pain and quality of life, and recent data indicated that it may also prevent the burden of cerebrovascular disease. In addition to ERT's clinical benefits, crucial topics like the most appropriate time to start therapy and the role of anti-drug antibodies (ADA) are analyzed. Treatment with agalsidase alfa in patients with FD substantially improves their outcomes and enhances their quality of life in patients with FD.

Efficacy and safety data (52-week) from a phase 1/2 trial and extension study of JR-171 (lepunafusp alfa) used in enzyme replacement therapy for patients with MPS I

Efficacy and safety data (52-week) from a phase 1/2 trial and extension study of JR-171 (lepunafusp alfa) used in enzyme replacement therapy for patients with MPS I

Incidence of fibrosing colonopathy with pancreatic enzyme replacement therapy in patients with cystic fibrosis

BackgroundHigh daily doses of pancreatic enzyme replacement therapy (PERT) were historically associated with risk of fibrosing colonopathy (FC) in people with cystic fibrosis (pwCF), leading to development of PERT dosing guidelines and reformulated products. This study quantified incidence of FC in pwCF treated with PERT following those measures. MethodsThis large prospective cohort study included eligible pwCF enrolled in the Cystic Fibrosis Foundation Patient Registry with ≥1 clinic visit in 2012–2014 and follow-up through 2020. Data on PERT exposure, demographics, and medical history were collected. Clinical data, imaging, and histopathology of suspected cases were examined by an independent adjudication panel of physicians familiar with this complication. ResultsBase Study Population included 26,025 pwCF who contributed 155,814 person-years [mean (SD) 6.0 (2.0) years] of follow-up. Over 7.8 years, 29 pwCF had suspected FC; three cases were confirmed by adjudication, 22 cases were confirmed as not FC, and four cases were indeterminate. There were 22,161 pwCF exposed to any PERT, with mean PERT use time of 5.583 person-years and mean daily dose of 8328 U lipase per kg per day. All three confirmed cases and four indeterminate cases of FC occurred during current use of PERT. Incidence rates per 1000 person-years exposed were 0.0242 (95 % CI [0.0050, 0.0709]) for confirmed FC and 0.0566 (95 % CI [0.0227, 0.1166]) for indeterminate or confirmed FC. ConclusionsThe incidence of FC in pwCF is very low in the era of current treatment guidelines and more stringent quality standards for PERT products.

Intracerebroventricular enzyme replacement therapy in patients with neuronopathic mucopolysaccharidosis type II: Final report of 5-year results from a Japanese open-label phase 1/2 study

Intravenous idursulfase is standard treatment for mucopolysaccharidosis II (MPS II) in Japan. In the interim analysis of this open-label, phase 1/2 study (Center for Clinical Trials, Japan Medical Association: JMA-IIA00350), intracerebroventricular (ICV) idursulfase beta was well tolerated, suppressed cerebrospinal fluid (CSF) heparan sulfate (HS) levels, and stabilized developmental decline over 100 weeks in Japanese children with MPS II. Here, we report the final study results, representing 5 years of ICV idursulfase beta treatment. Six male patients with MPS II and developmental delay were enrolled starting in June 2016 and followed until March 2021. Patients received up to 30 mg ICV idursulfase beta every 4 weeks. Outcomes included CSF HS levels, developmental age (DA) (assessed by the Kyoto Scale of Psychological Development), and safety (adverse events). Monitoring by laboratory biochemistry tests, urinary uronic tests, immunogenicity tests, and head computed tomography or magnetic resonance imaging were also conducted regularly. Following ICV idursulfase beta administration, mean CSF HS concentrations decreased from 7.75 μg/mL at baseline to 2.15 μg/mL at final injection (72.3% reduction). Mean DA increased from 23.2 months at screening to 36.0 months at final observation. In five patients with null mutations, mean DA at the final observation was higher than or did not regress compared with that of historical controls receiving intravenous idursulfase only, and the change in DA was greater in patients who started administration aged ≤3 years than in those aged >3 years (+28.7 vs −6.5 months). The difference in DA change versus historical controls in individual patients was +39.5, +40.8, +17.8, +10.5, +7.6 and − 4.5 (mean + 18.6). Common ICV idursulfase beta-related adverse events were vomiting, pyrexia, gastroenteritis, and upper respiratory tract infection (most mild/moderate). These results suggest that long-term ICV idursulfase beta treatment improved neurological symptoms in Japanese children with neuronopathic MPS II.

Investigation of bone mineral density and the changes by enzyme replacement therapy in patients with Fabry disease.

Fabry disease (FD) is an inherited disorder that causes organ dysfunction. However, only a few studies have reported on bone mineral density (BMD) in FD patients, and the relationship between BMD and clinical factors such as globotriaosylsphingosine (lyso-Gb3) remains unclear. Therefore, the current study sought to investigate BMD in FD patients, the relationship between BMD and lyso-Gb3, and the effects of enzyme replacement therapy (ERT) on changes in BMD and lyso-Gb3. This single-center, observational study included 15 patients who visited our facility for FD between January 2008 and June 2021. We assessed BMD and clinical characteristics in study patients, including plasma lyso-Gb3 levels, and examined the relationship between BMD and plasma lyso-Gb3 levels, and changes in BMD after starting ERT. Male patients' BMD had reduced, whereas female patients' BMD was preserved. Male patients had significantly higher plasma lyso-Gb3 levels than female patients. Moreover, plasma lyso-Gb3 levels were found to be significantly related to the lumbar spine and femoral BMD. These were strongly linked with plasma lyso-Gb3 levels in male patients, whereas no strong link was observed in female patients. Furthermore, BMD significantly increased only in male patients although plasma lyso-Gb3 levels significantly decreased by ERT in all patients. BMD decreased possibly due to Gb3 accumulation, and ERT could increase BMD in male FD patients.

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-science allowed computation of transcriptional landscapes from four nephron compartments and their integration with existing proteome and drug-target interactome data. Comparing these transcriptional landscapes revealed high inter-cohort heterogeneity. Kidney compartment transcriptional landscapes comprehensively reflected differences in FN cohort characteristics. With exception of a few aspects, in particular arteries, early ERT in patients with classical Fabry could lastingly revert FN gene expression patterns to closely match that of control individuals. Pathways nonetheless consistently altered in both FN cohorts pre-ERT were mostly in glomeruli and arteries and related to the same biological themes. While keratinization-related processes in glomeruli were sensitive to ERT, a majority of alterations, such as transporter activity and responses to stimuli, remained dysregulated or reemerged despite ERT. Inferring an ERT-resistant genetic module of expressed genes identified 69 drugs for potential repurposing matching the proteins encoded by 12 genes. Thus, we identified and cross-validated ERT-resistant gene product modules that, when leveraged with external data, allowed estimating their suitability as biomarkers to potentially track disease course or treatment efficacy and potential targets for adjunct pharmaceutical treatment.

At home enzyme replacement therapy for patients with lysosomal disorders: A single-centre experience

At home enzyme replacement therapy for patients with lysosomal disorders: A single-centre experience

Pancreatic Enzyme Replacement Therapy in Patients with Non-pancreatic Digestive Conditions: A Nationwide Claims Analysis.

Pancreatic enzyme replacement therapy (PERT) is most commonly used to treat exocrine insufficiency related to pancreatic diseases, but can be used for non-pancreatic digestive conditions (NPDC). We aimed to determine the prevalence of PERT use and describe prescription patterns in individuals with NPDC. A nationally representative claims database of 48.6 million enrollees was used to identify individuals who received PERT prescription(s) in the absence of any pancreas-related diagnosis. Data on demographics, enrolment, comorbidities, exocrine function testing, treatment and potential indications for PERT were retrieved, and compared with individuals who received PERT for primary diagnosis of chronic pancreatitis (CP). A total of 29,234 individuals (64.1% female, mean age 52.4 ± 16.5years) received PERT for NPDC. The overall estimated US population prevalence rate for PERT use for NDPC was 60.2/100,000 persons. Rates increased significantly with age and were higher in women in all age groups except 1-20years old. When compared with CP, individuals with NPDC receiving PERT were more likely to be older (52.4 vs. 50.1years), female (64.1% vs. 51.0%), have lower prevalence of alcoholism (3.6% vs. 25.0%), tobacco abuse (8.4% vs. 30.1%), and received PERT for shorter mean duration (5.3 vs. 8.2months) (all p < 0.001). Median dose of PERT in individuals with NPDC was 2880 lipase units/day. Although proportionally low, a sizable population receives PERT for NPDC. PERT for NPDC is usually prescribed at a low dose and for shorter duration, suggesting it is used mostly as a trial for or until resolution of symptoms.

Survival benefit of pancreatic enzyme replacement therapy in patients undergoing treatment of pancreatic neuroendocrine tumours

Treatment with somatostatin analogues (SSAs) or pancreaticoduodenectomy frequently causes malnutrition-inducing pancreatic exocrine insufficiency. This single-centre retrospective cohort study aimed to establish whether pancreatic enzyme replacement therapy (PERT) improves survival or nutritional status in SSA or pancreaticoduodenectomy-treated patients with pancreatic neuroendocrine tumours (pNETs). SSA and/or pancreaticoduodenectomy-treated patients with pNETs, diagnosed between 2009 and 2019, (n=77) were retrospectively identified from departmental databases. Data was sourced from clinical records. Overall survival and percentage monthly weight changes were compared between PERT-treated (n=45) and non-PERT-treated (n=32) patients. PERT-treated patients experienced significantly greater median monthly weight gain (+0.01% vs-0.10%, p=0.038) and 5-year survival (81% vs 51%, p=0.007). PERT was not, however, independently associated with survival (Hazard ratio 0.47, 95% CI 0.14-1.62, p=0.232). Considering SSA-treated patients (n=50) only, PERT-treated patients (n=24) showed numerically but non-significantly improved monthly weight gain (+0.04% vs-0.18%, p=0.139) and median survival (55.5, 95% CI 10.2-100.7 vs 42.4, 95% CI 11.7-73.2 months, p=0.082). PERT may improve survival and nutrition in SSA and pancreaticoduodenectomy-treated patients with pNETs, however, low patient numbers precluded the reliable mitigation of confounding in this study. A further multi-centre study is required to define the benefits of PERT in this population.

Prescription patterns of pancreatic enzyme replacement therapy for patients with pancreatic cancer in the United States.

Exocrine pancreatic insufficiency (EPI) is frequently seen in patients with pancreatic cancer (PDAC) and is thought to contribute to nutritional complications. While EPI can be pharmacologically temporized with pancreatic enzyme replacement therapy (PERT), there is lack of clear evidence informing its use in PDAC. Here we aim to survey pancreatic surgeons regarding their utilization of PERT in the management of EPI for PDAC. An online survey was distributed to the members of The Americas Hepato-Pancreato-Biliary Association (AHPBA) and The Pancreas Club. 86.5% (180/208) of surgeons prescribe PERT for at least some resectable/borderline resectable PDAC cases. Only a minority of surgeons order investigations to confirm EPI before starting PERT (28.1%) or test for adequacy of therapy (28.3%). Few surgeons believe that PERT has an effect on overall survival (19.7%) or disease-free survival (6.25%) in PDAC. PERT is widely prescribed in patients with resectable/borderline resectable PDAC, but investigations establishing EPI and assessing PERT adequacy are underutilized. A substantial proportion of surgeons are unclear as to the effect of PERT on survival outcomes in PDAC. These data call for prospective studies to establish guidelines for optimal use of PERT and its effects on survival outcomes in PDAC.

Effect of Anti-Iduronate 2-Sulfatase Antibodies in Patients with Mucopolysaccharidosis Type II Treated with Enzyme Replacement Therapy

To assess the relationship between anti-Iduronate 2-sulfatase (IDS) antibodies, IDS genotypes, phenotypes and their impact in patients with enzyme replacement therapy (ERT)-treated Mucopolysaccharidosis type II. Dutch patients treated with ERT were analyzed in this observational cohort study. Antibody titers were determined by enzyme-linked immunosorbent assay. Neutralizing effects were measured in fibroblasts. Pharmacokinetic analysis of ERT was combined with immunoprecipitation. Urinary glycosaminoglycans were measured using mass spectrometry and dimethylmethylene blue. Eight of 17 patients (47%) developed anti-IDS antibodies. Three patients with the severe, neuronopathic phenotype, two of whom did not express IDS protein, showed sustained antibodies for up to 10years of ERT. Titers of 1:5120 or greater inhibited cellular IDS uptake and/or intracellular activity invitro. In 1 patient who was neuronopathic with a titer of 1:20 480, pharmacokinetic analysis showed that all plasma recombinant IDS was antibody bound. This finding was not the case in 2 patients who were not neuronopathic with a titer of 1:1280 or less. Patients with sustained antibody titers showed increased urinary glycosaminoglycan levels compared with patients with nonsustained or no-low titers. Patients with the neuronopathic form and lack of IDS protein expression were most at risk todevelop sustained anti-IDS antibody titers, which inhibited IDS uptake and/or activity invitro, and the efficacy of ERT in patients by lowering urinary glycosaminoglycan levels.

MO024: Effect of green tea on top of enzyme replacement therapy in patients with Fabry disease: a molecular biology approach

Abstract BACKGROUND AND AIMS Fabry disease (FD) is an X-linked rare disease characterized by deficient expression and activity of alpha-galactosidase A and consequent lysosomal accumulation of Gb3 and derivatives in various organs. Notwithstanding the first-line treatment with enzyme replacement therapy (ERT), FD progresses with serious cardiovascular, renal and cerebral implications in particular in case of late diagnosis. This suggests the involvement of secondary parallel mechanisms to Gb3 accumulation. We have shown that FD patients have increased and active oxidative stress (OxSt), which plays a primary role in the induction of cardiovascular–renal remodeling and contributes in these patients to the associated left ventricular hypertrophy (LVH). We have also shown that in dialysis and CKD stage 3–4 patients, another population with high cardiovascular risk, antioxidant treatment with green tea significantly reduced OxSt-related cell signaling mechanisms improving LVH. We have therefore hypothesized that inpatients with FD, green tea on top of ERT might have additive positive effects toward OxSt and OxSt-induced cardiovascular–renal remodeling using a molecular biologic approach. METHOD Ten naïve Fabry patients were enrolled and evaluated ex vivo in mononuclear cells the status of OxSt before ERT, after 12 months of ERT and after 6 months of the additional treatment with two capsules of green tea (600 mg Camellia Sinensis leaves dry extract, 40% Epigallocathechinegallate, Frama S.r.l., Noventa Padovana, Italy) per day taken in the morning at fast on top of ERT. The OxSt was evaluated and compared in the tree time periods in terms of protein expression of p22phox (subunit of NADH/NADPH oxidase essential for the production of superoxide), phosphorylation state of MYPT-1 (regulatory subunit of the myosin light chain phosphatase), ERK 1/2 (effectors at nuclear level of cardiovascular remodeling) and plasma levels of MDA (marker of lipid peroxidation). HO-1 levels (antioxidant and protective from OxSt) were also evaluated. RESULTS p22phox was significantly decreased after 12 months of enzymatic therapy and further decreased after 6 months of green tea treatment (1.91 ± 0.83 versus 1.10 ± 0.23 versus 0.83 ± 0.20 d.u.), same for MYPT-1 phosphorylation (0.81 ± 0.20 versus 0.68 ± 0.21 versus 0.52 ± 0.11 d.u.). The phosphorylation of ERK 1/2 remained unchanged after 12 months of ERT, but significantly decreased after 6 months of green tea supplementation (1.06 ± 0.24 versus 1.02 ± 0.27 versus 0.76 ± 0.14 d.u.) as well as MDA levels (5.50 ± 1.08 versus 5.10 ± 1.1 versus 4.16 ± 0.86 nmol/mL). Finally, HO-1 significantly increased with both ERT and green tea supplementation (1.37 ± 0.34 versus 1.67 ± 0.51 versus 1.96 ± 0.53 ng/mL). CONCLUSION This study provides data pointing toward an antioxidant effect exerted by ERT itself, which is further amplified by the treatment with green tea on top of ERT. These data while on one hand highlight the fundamental importance of an early diagnosis and treatment of FD, on the other hand suggest the need of adjuvant antioxidant treatments to prevent or improve specific disease manifestations.

The need for home enzyme replacement therapy for patients with lysosomal disease in Japan

The need for home enzyme replacement therapy for patients with lysosomal disease in Japan

Defining the role of Lyso-Gb1 as a biomarker over 12 months after first initiation of enzyme replacement therapy in patients with Gaucher disease in LYSO-PROVE study

Defining the role of Lyso-Gb1 as a biomarker over 12 months after first initiation of enzyme replacement therapy in patients with Gaucher disease in LYSO-PROVE study