Therapeutic Targeting to Bone: Enzyme Replacement Treatment for Hypophosphatasia

Abstract The fifth SEE meeting on rare diseases (RDs) was held in Macedonian Academy of Sciences and Arts (MASA) the November 11th, 2016. Several lectures dealt with mucopolysaccharidosis, glycogen storage diseases and the possibilities for their diagnosis and treatment. Enzyme replacement treatment (ERT), its availability, effects (or the lack of it) on the brain, and further prospects of eventual gene treatment were comprehensively exposed and discussed. Special accent was on Gaucher, Morquio IVA, Hunter and the audience was given new knowledge on the complexities of diagnosis and treatment. A block of lectures on rare renal diseases was also impressive. From renal stones, their molecular and genetic mechanisms to different forms of CAKUT the use of NGS and other molecular methods in diagnosis of RDs. Mitochondrial diseases, the novelties and importance of early discovery were comprehensively exposed. Special lecture was given on the complement system. Endocrine disruptors, microprolactinomas were also the topic of the meeting. A rather reach session of posters was also presented.

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CD77 levels over enzyme replacement treatment in Fabry Disease Family (V269M)

Brazilian Journal of Nephrology ◽

10.1590/2175-8239-jbn-3910 ◽

2018 ◽

Vol 40 (4) ◽

pp. 333-338

Author(s):

Ester Miranda Pereira ◽

Adalberto Socorro da Silva ◽

Raimundo Nonato da Silva ◽

José Tiburcio Monte Neto ◽

Fernando F. do Nascimento ◽

...

Keyword(s):

Fabry Disease ◽

Cell Types ◽

Control Group ◽

Gene Encoding ◽

Peripheral Blood Mononuclear ◽

Enzyme Replacement ◽

Replacement Treatment ◽

Promising Tool ◽

Potential Marker ◽

Different Cell Types

ABSTRACT Introduction: Fabry disease (FD) is a disorder caused by mutations in the gene encoding for lysosomal enzyme α-galactosidase A (α-GAL). Reduced α-GAL activity leads to progressive accumulation of globotriaosylceramide (Gb3), also known as CD77. The recent report of increased expression of CD77 in blood cells of patients with FD indicated that this molecule can be used as a potential marker for monitoring enzyme replacement therapy (ERT). Objective: The purpose of this study was to evaluate the CD77 levels throughout ERT in FD patients (V269M mutation). Methods: We evaluated the fluctuations in PBMC (peripheral blood mononuclear cell) membrane CD77 expression in FD patients undergoing ERT and correlated these levels with those observed in different cell types. Results: A greater CD77 expression was found in phagocytes of patients compared to controls at baseline. Interestingly, the variability in CD77 levels is larger in patients at baseline (340 - 1619 MIF) and after 12 months of ERT (240 - 530 MIF) compared with the control group (131 - 331 MFI). Furthermore, by analyzing the levels of CD77 in phagocytes from patients throughout ERT, we found a constant decrease in CD77 levels. Conclusion: The increased CD77 levels in the phagocytes of Fabry carriers together with the decrease in CD77 levels throughout ERT suggest that measuring CD77 levels in phagocytes is a promising tool for monitoring the response to ERT in FD.

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Adult Fabry patients in Sweden - Baseline data and Outcome of Four-Year Enzyme Replacement Treatment in a Male Cohort without Proteinuria

JMED Research ◽

10.5171/2015.373829 ◽

2015 ◽

pp. 1-15

Author(s):

Jan-Ove Johansson ◽

◽

Jarl Ahlmén ◽

Anita Persson ◽

Kenneth Caidahl ◽

...

Keyword(s):

Baseline Data ◽

Enzyme Replacement ◽

Replacement Treatment ◽

Male Cohort

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Bone Biomarkers in Mucopolysaccharidoses

International Journal of Molecular Sciences ◽

10.3390/ijms222312651 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12651

Author(s):

Akari Nakamura-Utsunomiya

Keyword(s):

Bone Metabolism ◽

Daily Living ◽

Endochondral Ossification ◽

Bone Growth ◽

Bone Biomarkers ◽

Enzyme Replacement ◽

Replacement Treatment ◽

Bone Disorder ◽

New Biomarkers ◽

And Cartilage

The accumulation of glycosaminoglycans (GAGs) in bone and cartilage leads to progressive damage in cartilage that, in turn, reduces bone growth by the destruction of the growth plate, incomplete ossification, and growth imbalance. The mechanisms of pathophysiology related to bone metabolism in mucopolysaccharidoses (MPS) include impaired chondrocyte function and the failure of endochondral ossification, which leads to the release of inflammatory cytokines via the activation of Toll-like receptors by GAGs. Although improvements in the daily living of patients with MPS have been achieved with enzyme replacement, treatment for the bone disorder is limited. There is an increasing need to identify biomarkers related to bone and cartilage to evaluate the progressive status and to monitor the treatment of MPS. Recently, new analysis methods, such as proteomic analysis, have identified new biomarkers in MPS. This review summarizes advances in clinical bone metabolism and bone biomarkers.

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