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Download a study on cell culture model
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Treatment of mucopolysaccharidoses by combination of various approaches: a study on cell culture model Izabela Chmielarz, Laboratory of Genomics and Human Genetics, Department of Molecular Biology, Faculty of Biology Supervisor: prof. dr hab. Grzegorz Węgrzyn, Department of Molecular Biology Co-supervisor: prof. dr hab. Ewa Łojkowska, Department of Biotechnology Mucopolysacharidoses (MPS) are a group of inherited metabolic diseases characterized by accumulation of glycosaminoglycans (GAG) in lysosomes. These usually fatal disorders are caused by mutations in genes coding for enzymes involved in degradation of GAGs. The deficiencies in activity of appropriate lysosomal enzymes result in various clinical phenotypes which include organomegaly, dysostis multiplex, decreased growth and respiratory insufficiency, and in some cases the central nervous system (CNS) is also affected. Mucopolysaccharidoses are divided into seven distinct types and 11 subtypes depending on the deficient enzyme. Due to progressive characteristic of these diseases early diagnosis and treatment at the early stages is crucial. There are various therapeutic approaches: enzyme replacement therapy, heamatopoietic stem cell transplantation, small synthetic chaperones, gene therapy, stop codon read-through strategy and substrate deprivation therapy (SDT). In our laboratory a detailed study have been conducted upon using genistein, a soy isoflavone, in reducing synthesis and accumulation of GAGs in MPS type III. Recent studies on specific inhibition of GAG synthesis using siRNA (small interfering RNA) have highlighted possible therapeutic applications for MPSs. That is why, we aimed to compare the effects of different treatment methods and their combinations on the reduction of GAG storage. We have assessed the effectiveness of siRNA-mediated silencing of genes coding for enzymes involved in the initial steps of GAG synthesis in comparison with the enzyme replacement therapy for MPS treatment and a combination of these methods. We have as well explored possible beneficial effects of combined enzyme replacement therapy and substrate deprivation therapy based on inhibition of GAG synthesis by genistein.
