Tesis doctoral de Luciano Matías Sobrevals
Previous studies have demostrated that the administration of recombinant igf-i protein is effective in the treatment of liver cirrhosis. However, the short half life of igf-i in serum and the high price of recombinant igf-i protein production, make this treatment exceedingly costly. Therefore, we have analyzed the therapeutic effect in liver cirrhosis of igf-i gene transfer using viral vectors. We have used recombinant viral vectors expressing rat igf-i based on simian virus 40 (rsvigf-i) or adeno-associated vectors (raavigf-i). We have inyected these vectors before or after cirrhosis induction in rats. Cirrhosis has been developed by intragastric administration of ccl4. Both pretreatment and treatment of liver cirrhosis with rsvigf-i or raavigf-i induced a curative process that resulted in improved liver functionality and decreased liver fibrosis. This therapeutic effect seems mediated by the igf-i-dependent induction of cytoprotective and antifibrogenic molecules and the inhibition of profibrogenic factors. Thus, igf-i expression reprograms the liver from a ¿scar formation¿ program, which leads to cirrhosis, to a ¿tissue repair¿ circuit that favours cirrhosis regression. Surprisingly, therapy was less efficient when rsvigf-i or high doses of aavigf-i were used. None of the vectors showed toxic effects in cirrhotic or healthy animals. The therapeutic effects observed with low doses of aav vectors expressing igf-i allows us to suggest that these vectors could base a useful therapy for patients that deteriorate in the waiting list for liver transplantation or for those patients non-suitable for liver transplant.
Datos académicos de la tesis doctoral «Análisis del efecto terapéutico y los mecanismos moleculares inducidos por vectores virales que expresan el factor de crecimiento similar a la insulina de tipo i (igf-i) en el tratamiento de la cirrosis hepática«
- Título de la tesis: Análisis del efecto terapéutico y los mecanismos moleculares inducidos por vectores virales que expresan el factor de crecimiento similar a la insulina de tipo i (igf-i) en el tratamiento de la cirrosis hepática
- Autor: Luciano Matías Sobrevals
- Universidad: Navarra
- Fecha de lectura de la tesis: 23/10/2009
Dirección y tribunal
- Director de la tesis
- María Purificacion Fortes Alonso
- Tribunal
- Presidente del tribunal: ignacio Torres alemán
- cristina Fillat fonts (vocal)
- ramon Bataller alberola (vocal)
- Jorge augusto Quiroga vilas (vocal)
