Enzyme and Gene Therapy Using Oxalate Degrading Enzyme for Kidney Stone Treatment

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Urolithiasis and calcium oxalate crystal deposition are metabolic disorders in vertebrates, including humans, primarily due to a lack of the oxalate catabolizing enzyme. The high intake of oxalate-rich foods often leads to this condition, which is very common in about 12% of the world population (Malik et al., 1998). It is also widely reported in the northwestern part of India. This problem is related to the fact that a portion of the human population is unable to properly metabolize oxalate, a condition that may result in the formation of kidney stones in those persons. Some green leafy vegetables (e.g., amaranth, spinach, rhubarb, and strawberries) are rich sources of vitamins and minerals, but they contain oxalic acid as a nutritional stress factor. Such plants, when consumed in large quantities, become toxic to humans because oxalate chelates calcium, and precipitation of calcium oxalate in the kidney leads to hyperoxaluria and destruction of renal tissues (Luque de Castro, 1988, Hodgkinson, 1970). There are no drug-based therapies for these conditions, so there is a lot of interest in studying oxalate metabolism and the enzymes that are involved in the biosynthesis and degradation of oxalate. A number of enzymes have evolved in plants (oxalate oxidase), fungi (oxalate decarboxylase), and bacteria (oxalyl-coA decarboxylase, formyl-coA: oxalate transferase) that degrade oxalate to formate and carbon dioxide. Enzymes that metabolize oxalic acid do not exist in human beings. Therefore, once oxalate is ingested or produced, it must be excreted through the kidneys because no gastrointestinal route of oxalate excretion is known (William and Wilson 1990). Oxalate decarboxylase from F. velutipes degrades oxalic acid to formic acid and carbon dioxide. The gene encoding oxalate decarboxylase has already been cloned (Mehta and Datta, 1991, Mehta, 1992). The study's goal was to use biodegradable polymers to deliver Oxalate decarboxylase to Sprague-Dawley rats with experimentally induced kidney stones in order to lower plasma and urinary oxalate concentrations. The whole work has been separated into two chapters. Chapter 1 pertains to the History of Polymers in Medicine, Therapeutic Use of Fungi, Oxalic Acid, and Enzyme Technologies, including Enzyme Therapy, Materials and Methods, Results, Discussion, Summary, and References, followed by Appendix I, II, and III.