Use of gc-1 in transplant related population

Abstract

Methods are disclosed for the use of GC-1 (sobetirome), a prodrug thereof, or a pharmaceutically acceptable salt or prodrug thereof to increase liver regeneration and healing in liver transplant donors and recipients.

We claim: 
     
         1 . A method for increasing hepatocyte cell number and mass in a liver of a liver transplant donor, comprising
 selecting a subject has donated a portion of their liver; and   administering to the subject an effective amount of a pharmaceutical composition comprising GC-1 (sobetirome) or a pharmaceutically acceptable salt thereof, wherein the pharmaceutical composition is administered to the subject within one day after a resection of the portion of their liver, and is continued for at most three weeks following the resection of the portion of their liver;   thereby increasing hepatocyte cell number and mass in the liver of the subject.   
     
     
         2 . The method of  claim 1 , wherein the subject is a high risk donor. 
     
     
         3 . The method of  claim 1 , wherein the subject is older than about 45 years of age. 
     
     
         4 . The method of  claim 1 , wherein the GC-1 or the pharmaceutically acceptable salt thereof is administered intravenously to the subject. 
     
     
         5 . The method of  claim 4 , wherein the GC-1 or the pharmaceutically acceptable salt thereof is administered at a dose of 0.1 mg/kg to about 0.5 mg/kg. 
     
     
         6 . The method of  claim 5 , the GC-1 or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg/kg. 
     
     
         7 . The method of  claim 1 , wherein the GC-1 or the pharmaceutically acceptable salt thereof is administered orally to the subject. 
     
     
         8 . The method of  claim 1 , wherein the GC-1 or the pharmaceutically acceptable salt thereof is administered for at most 14 days after liver transplantation. 
     
     
         9 . The method of  claim 1 , further comprising monitoring the metabolic function of the liver in the subject. 
     
     
         10 . The method of  claim 1 , further comprising measuring liver size in the subject. 
     
     
         11 . The method of  claim 1 , further comprising obtaining a lipid profile of the subject. 
     
     
         12 . The method of  claim 1 , wherein the subject is human. 
     
     
         13 . The method of  claim 1 , wherein the GC-1 or the pharmaceutically acceptable salt thereof is administered within one day of the donation of their liver. 
     
     
         14 . The method of  claim 1 , wherein the GC-1 or the pharmaceutically acceptable salt thereof is administered orally, and the subject is human. 
     
     
         15 . The method of  claim 14 , wherein 10 μg to 100 μg of GC-1 or the a pharmaceutically acceptable salt thereof is administered once, twice or three times per day. 
     
     
         16 . The method of  claim 1 , wherein the GC-1 or the pharmaceutically acceptable salt thereof is administered for seven to fourteen days following the resection of the liver in the subject. 
     
     
         17 . The method of  claim 1 , wherein hepatocyte proliferation is measured by radiological monitoring of hepatic size in the subject. 
     
     
         18 . The method of  claim 1 , further comprising measuring an increase in hepatocyte cell number in the subject. 
     
     
         19 . A method for increasing hepatocyte cell number and mass in a liver of a subject that has hepatoxicity due to an acetaminophen overdose, comprising
 selecting the subject that has hepatoxicity due to an acetaminophen overdose, and   administering to the subject that has hepatoxicity due to the acetaminophen overdose an effective amount of a pharmaceutical composition comprising GC-1 (sobetirome) or a pharmaceutically acceptable salt thereof, wherein the pharmaceutical composition is administered to the subject within 72 hours of the acetaminophen overdose;   thereby increasing hepatocyte cell number and mass in the liver of the subject.   
     
     
         20 . A method for increasing hepatocyte cell number and mass in a liver transplant in a subject, comprising
 selecting a subject that is the recipient of a liver transplant, wherein the subject has small for size syndrome (SFSS);   administering to the subject an effective amount of a pharmaceutical composition comprising GC-1 (sobetirome) or a pharmaceutically acceptable salt thereof, wherein the pharmaceutical composition is administered to the subject within one day after liver transplantation and is continued for at most three weeks following the liver transplantation;   thereby increasing hepatocyte cell number and mass in the liver transplant in the subject.