United States : Inventive Approach May Improve Enzyme Replacement Therapy For Fabry Disease.Byline: pinto03 A new study uses a creative structure-based remodeling remodeling /re·mod·el·ing/ (re-mod´el-ing) reorganization or renovation of an old structure. bone remodeling strategy to design a therapeutic protein that exhibits significant advantages over currently available treatments for a rare disease that often leads to cardiac and renal failure renal failure n. Acute or chronic malfunction of the kidneys resulting from any of a number of causes, including infection, trauma, toxins, hemodynamic abnormalities, and autoimmune disease, and often resulting in systemic symptoms, especially edema, . The research, published by Cell Press on October 22nd in the American Journal of Human Genetics The American Journal of Human Genetics is a leading journal in the field of human genetics. Since its inception in 1948 by the American Society for Human Genetics, the Journal has provided a record of research and review relating to heredity in humans and to the application , describes a new and highly promising candidate for enzyme replacement therapy Enzyme replacement therapy is a medical treatment replacing an enzyme in patients in whom that particular enzyme is deficient or absent. Usually this is done by giving the patient an intravenous (IV) infusion containing the enzyme. (ERT ERT abbr. estrogen replacement therapy Estrogen replacement therapy (ERT) A treatment in which estrogen is used therapeutically during menopause to alleviate certain symptoms such as hot flashes. ) for Fabry disease. Fabry disease is a rare genetic disorder caused by a deficiency in alpha-galactosidase-A (GLA), an enzyme that breaks down fatty substances called glycolipids. Without the proper level of enzyme activity Enzyme activity A measure of the ability of an enzyme to catalyze a specific reaction. Mentioned in: Glucose-6-Phosphate Dehydrogenase Deficiency , a glycolipid Glycolipid One of a class of compounds having solubility properties of a lipid and containing one or more molecules of a covalently attached sugar. called globotriaosylceramide (Gb3) accumulates to harmful levels inside cellular structures called lysosomes lysosomes (līs  sōmz),n the self-contained organelles found inside most cells, which contain hydrolytic enzymes that aid in intracellular digestion. and damages the skin, nerves, eyes, kidneys and cardiovascular system. Although scientists have generated GLA for ERT, thus far this approach has proved challenging. "Many patients have been successfully treated with these manufactured GLA proteins, but there are still problems to be resolved," explains senior study author Dr. Hitoshi Sakuraba from Meiji Pharmaceutical University in Tokyo. "For example, these enzymes are unstable in the blood, do not effectively reach the kidneys and heart and frequently cause an allergic reaction in Fabry patients." Dr. Sakuraba and colleagues took a different approach and, instead of making recombinant GLA, attempted to alter a different enzyme, called ?-N-acetylgalactosaminidase (NAGA), so that it could function like GLA. Normally, NAGA catalyses the hydrolysis hydrolysis (hīdrŏl`ĭsĭs), chemical reaction of a compound with water, usually resulting in the formation of one or more new compounds. of a different type of substrate and does not recognize the same substrates as GLA. Importantly, although NAGA is structurally similar to GLA, it does not react with the immune system in the same way. The researchers examined the structures of GLA and NAGA and predicted how to alter NAGA so that it would recognize GLA substrates. Because the overall structure of NAGA was not changed, it was not expected to cause an allergic reaction in Fabry patients. The modified NAGA was found to be more stable than recombinant GLA and exhibited characteristics necessary for efficient incorporation into cells. "Following confirmation of the effect of modified NAGA on cultured Fabry cells, we injected it into Fabry mice, and examined the incorporation of the enzyme into organs and its Gb3-degrading activity," explains Dr. Sakuraba. The modified NAGA was successfully incorporated into the liver, kidneys and the heart and there was a decrease in Gb3 accumulation in these organs. "The enzyme has many advantages because of it high stability and the low possibility of the occurrence of an allergic reaction, although these characteristics should be confirmed in clinical studies in the future," concludes Dr. Sakuraba. "The modified NAGA is highly promising as a new enzyme for ERT for Fabry disease, and such structure-based designing of modified enzymes should be useful for the development of ERT for lysosomal s Copyright : Euclid Infotech Pvt. Ltd. Provided by Syndigate.info an Albawaba.com company |
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