Reversal Of Diabetes In Pigs Using Liver-directed Gene Therapy
Funder
National Health and Medical Research Council
Funding Amount
$573,807.00
Summary
Type I diabetes mellitus is caused by the autoimmune destruction of the beta cells of the pancreas that secrete insulin. We have shown that we can cure diabetes in spontaneously diabetic mice by delivery of the insulin gene to the liver using a non-pathogenic viral delivery system. The study aims to repeat this work in pigs which have similar physiology to humans. If successful this would be proof-of-principle that we could theoretically control blood glucose levels in humans.
Many people with organ failure such as heart or kidney disease need a transplant to survive. In the case of kidney failure patients can be kept alive by the artificial kidney however this sort of mechanical traeatment is much less satisfactory than a transplant. Unfortunately most patients who would benefit from a transplant are unable to receive one beacuse of the shortage of living or cadaver donors. A possible solution to this shortage of organs for transplantation is to use animal organs. Pi ....Many people with organ failure such as heart or kidney disease need a transplant to survive. In the case of kidney failure patients can be kept alive by the artificial kidney however this sort of mechanical traeatment is much less satisfactory than a transplant. Unfortunately most patients who would benefit from a transplant are unable to receive one beacuse of the shortage of living or cadaver donors. A possible solution to this shortage of organs for transplantation is to use animal organs. Pigs are the most suitable animal donor. However, a pig-to-human organ is rejected immediatly because of the distance between the species. Over the last 10 years, we and others have been trying to understand which genetic differences are important. It is now clear that there are several important differences. One of these is a Blood Group like molecule in the pig that humans react with immediatly on transplantation. This is called the Gal molecule. We and others have been successful in removing the pig gene that makes this molecule. In addition we have added several human genes to pigs to prevent the early vigorous rejection which usually occurs. Organs from these genetically modified pigs have been tested by transplantation into baboons and monkeys. The transplants which used to be rejected within minutes, now survive for months. However, they organs are still rejected by a process which causes clotting in the transplanted organs. We now understand the mechanism andare making genetically modified pigs with human genes which regulate clotting of human blood. This project will test organs from these pigs by transplantation into baboons. We will also make a special strain of pigs in which all these genetic modifications are assembled. This involves the removal of one pig gene and the addition of 4 or 5 human genes. We think it is highly likely that this combination of genetic modifications will make this strain of pigs much more suitable as organ donors.Read moreRead less