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of the drug, its place in therapy, and especially its cost-benefit ratiowill become critical in the product's success. |
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Gene manipulation strategies may lie at the core of disease treatment. It seems that not a day goes by without a new gene being discovered that is the cause of a well-known disease. That there would be a single gene responsible for a metabolic disease like gout or homocystinuria, for example, seems reasonable. That a single gene mutation could cause a condition like Eulers Danos syndrome also seems reasonable. But breast cancer, lupus erythematosus, or coronary artery disease caused by a single abnormal gene is a surprise to say the least. A building body of evidence supports many of these claims. This is exciting and may represent a new age of possible effective therapies for some of the most important conditions affecting man. But the identification of the gene itself, though an important first step, is only the initial part of a very long process to cure the disease. The techniques for gene modification are rudimentary and certainly need further study. An area of cardiology where gene therapy should be most promising is restenosis following acute angioplasty. Angioplasty entails placing a catheter in the coronary vessel, inflating a balloon at the tip of the catheter, pushing aside the atherosclerotic lesion. This is rather a successful technique; however, a major problem limiting the success of angioplasty is reocclusion. At the time of the initial angioplasty, there are stimuli that are initiated that cause cell proliferation of the media leading to restenosis. The medial cells that proliferate are very homogeneous, and this process seems to occur quite rapidly and in 2060% of individuals having a single-vessel angioplasty. But even this simple model for gene therapy has proven a difficult target. There has been some very interesting work done with antisense therapy with promise shown in the area of restenosis. Clinical trials are currently in progress using antisense material. However so much of the methodology is new, and this impedes the clinical development. The use of viral vector to insert the material in the medial cells turning off protein synthesis is one limitation. A major question arises, can the virus replicate? Will the gene be correctly inserted or will additional genetic material of the virus be inserted? Thus, the validation and safety aspects are formidable and can markedly slow the development process. As experience increases with product development and manufacture and guidance for developing clinical trials improves, the overall time for developing gene manipulation strategies will be improved. We are only at the frontiers of gene manipulation; the possibilities are phenomenal. Will the promise be realized? This question cannot be answered at this time, but the prospect of preventing diseases of such great magnitude |
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