DOWN-REGULATION OF A HARMFUL VARIANT PROTEIN BY REPLACEMENT OF ITS NORMAL-PROTEIN

To compensate for the hypoprotein and hypoalbuminemia of familial amyl oidotic polyneuropathy (FAP) patients, 800 ml of fresh frozen plasma ( FFP) was intravenously administered and change in total and variant tr ansthyretin (TTR) levels were measured in the plasma. After injection of FFP, total plasma TTR levels were elevated and variant TTR levels d ecreased from 24 to 48 h, accompanied by an elevation of plasma total protein, albumin levels and TTR levels, To elucidate the mechanism of this phenomenon, a large amount of purified normal TTR from normal hum an plasma was intravenously injected in mice and FAP patients. By intr avenous injection of 3 mg of the purified TTR to C57Black6, the expres sion of TTR mRNA decreased from 6 to 24 h post injection, and graduall y increased up to 48 h post injection. After injecting 400 mg of norma l TTR in each of 3 FAP patients, total plasma TTR levels were elevated and variant TTR levels decreased significantly from 24 to 48 h. These results suggested that down regulation of the harmful protein by repl acement of its normal form of the protein occurred by this method. Thi s phenomenon should be applied as the basis for one of the useful meth ods for decreasing the harmful proteins in the circulation. (C) 1997 E lsevier Science B.V.