H2020Индивидуална стипендия2018–2020

LYSOBONE · Cellular and molecular analysis of the skeletal pathologies associated with mucopolysaccharidosis-VI (MPS-VI)

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2018-03-01 → 2020-02-29
Финансиране от ЕС: 159 461 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Ефектът от ензимна терапия при мукополизахаридоза тип VI се анализира чрез модел с мишки, за да се проследят промените в скелета и клетките. Това помага да се разберат причините, поради които сегашното лечение не е напълно ефективно.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Cellular and molecular analysis of the skeletal pathologies associated with mucopolysaccharidosis-VI (MPS-VI)

Within the LYSOBONE project, the overall goal was to investigate and understand the effects of enzyme replacement therapy (ERT) for the lysosomal storage disorder mucopolysaccharidosis type VI (MPS-VI). As MPS-VI in patients is caused by inactivating mutations in the ARSB gene, resulting in a deficiency for the lysosomal enzyme ARSB, MPS-VI patients are currently being treated with a human recombinant form of ARSB (rhARSB, Naglazyme®) through ERT. It has however always been clear that ERT in these patients does not fully correct or prevent the development of the disorder, a problem for which the underlying mechanisms remained unknown and poorly investigated. Moreover, since the current treatment options for MPS-VI patients, especially conventional ERT, do not only have their limitations, but are also very expensive, the LYSOBONE project had a potentially high impact on life quality of the patients and their parents and the health care system. To achieve the overall goal of the LYSOBONE project, several scientific and training objectives were defined. The overall scientific objective of the project was the full characterization of the skeletal and non-skeletal effects of Arsb deficiency and the impact of ERT with rhARSB in Arsb-deficient, a mouse model for MPS-VI. Another major objective was to unravel the cellular consequences of Arsb deficiency at a molecular level and to investigate mechanisms of rhARSB uptake and lysosomal delivery in different cell types. This project also had several training objectives, to improve my scientific and methodological knowledge, presentation skills, writing skills, language and administrative skills. Overall, the data obtained within the LYSOBONE project, allow us to conclude that defects in many skeletal cell types are prevented and corrected by ERT in a valid mouse model for MPS-VI, whereas specifically chondrocyte defects are not targeted by ERT. This knowledge provides the basis to specifically improve chondrocyte delivery of the recombinant enzyme as well as patient monitoring. Future research towards novel therapeutic approaches could therefore not only provide improved treatment efficiency for MPS-VI patients, but possibly also a more affordable alternative than conventional ERT.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Mucopolysaccharidosis-VI (MPS-VI) is a lysosomal storage disorder predominantly affecting skeletal remodelling and caused by pathogenic mutations in the ARSB gene, encoding the glycosaminoglycan-degrading enzyme arylsulfatase B. Preliminary analysis of Arsb-deficient mice unraveled a skeletal phenotype of similar severity and with lysosomal storage defects in different skeletal cell types. This Arsb-deficient mouse model therefore provides an excellent tool to understand the skeletal and non-skeletal pathologies related to MPS-VI and to address the clinically relevant question, if enzyme replacement therapy (ERT) can influence the existing (non-)skeletal pathologies in lysosomal storage disorders. Moreover, another major objective is to unravel the cellular consequences of Arsb-deficiency on a molecular level and to investigate mechanisms of ARSB uptake and lysosomal delivery in different primary cell types of Arsb-deficient mice. This project will therefore certainly generate knowledge with relevance for other (skeletal) disorders as well, as the cellular defects in MPS-VI are closely linked to that of two of the most prevalent disorders in the European Union, i.e. osteoporosis and osteoarthritis. Next to its scientific goals, this proposal aims to offer a broad personal training program for me as a postdoctoral researcher as well. Handling this project will not only offer an intensive scientific training (intellectual-methodological), but also improve my skills regarding project management (administrative-financial) and writing. As a two-way transfer, my previously acquired knowledge on the genetics of skeletal disorders and related experimental skills will be transferred to the host organization. A final goal of this proposal is to disseminate the acquired data towards specialized scientific audiences (scientific conferences and publications) and propagate these data towards non-expert audiences (patient meetings, press releases) as well.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITAETSKLINIKUM HAMBURG-EPPENDORF · HamburgКоординаторГермания