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[摘要]：Liver transplantation as a treatment for transthyretin amyloidosis (ATTR) was introduced 20 years ago and is currently the only available treatment for the disease. Although the procedure has been proven to halt the progression of the disease for most patients, several unexpected complications have emerged, and it is obvious that for several mutations liver transplantation has no impact on the progression of the disease. Heart complications, especially in elderly patients, have been a cause of concern for many patients, including those with the most widespread neuropathic mutation, transthyretin (TTR)Val30Met. These drawbacks and the risk involved with transplantation, together with the need for life-long immunosuppressive therapy, have demonstrated the need for an effective medical treatment. From the experience with liver transplant patients, it appears that the amyloidogenic properties of wild-type TTR are enhanced once amyloid formation has started, and that elimination of the mutated TTR is not sufficient to prevent further amyloid formation in all cases. The development of animal models for the disease has further increased our understanding of factors involved in amyloid formation, and offers the possibility to test new medical treatment modalities. From our experience with liver transplantation, it appears that treatment directed towards stabilizing the TTR tetramer, eliminating misfolded TTR, decreasing TTR serum concentrations, decreasing toxicity and removing amyloid deposits are the most attractive modalities for treatment. Several studies are currently planned or ongoing to explore these possibilities, and promising results are already being reported. |
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