Gene Therapy: How Gene Therapy Could Cure Liver Disease

Gene therapy is a medical procedure in which the cell genetic structure is manipulated or modified by adding one or more genes to bring about a desired result. It can be used to cure or treat diseases or illnesses that have been caused either by malfunctioning genes or by the absence of certain essential genes in the cells.

In gene therapy, researchers first isolate the required genes, combine these with a specially selected virus and, using this virus vector tool, transduce them into the targeted cells. The virus used is one that poses no risk of copying itself or infecting other people. The virus vector transfer process can be done directly in the cells of a living organism or in a cell culture. The virus vector delivers the gene into the cell and this gene then assists the cell in carrying out its specific functions correctly.

Medical researchers are exploring the possibility of treating liver disease using gene therapy. Symptoms of liver disease (a term that covers numerous conditions arising as a result of a diseased or defective liver) can range from jaundice to skin rashes, headaches, mood swings, and digestive problems.

The Crigler-Najjar Syndrome is an inherited liver condition caused by the absence of a crucial gene that assists with cell detoxification. Without this gene, the liver cells cannot get rid of bilirubin. Bilirubin, which is hemoglobin waste, then accumulates to high levels in the blood. This results in jaundice and sometimes even brain damage.

The usual treatment for this condition is to expose the patient to UV lights over a long period of time. Now researchers at the Baylor College of Medicine have pointed to the possibility of gene therapy curing or at least holding the disease at bay.

Experimenting on rats, they isolated and removed the required gene from the liver of a healthy rat, and using an adenovirus as virus vector, inserted the gene into rats with the Crigler-Najjar Syndrome. The diseased rats were cured after one single injection.

The researchers hope that gene therapy will have a similar positive effect on humans as well. They are currently carrying out more research to make sure that this gene therapy is completely safe for human use.

Another inherited liver disorder is the glycogen storage disease type 1a (GSD-1a) or von Gierke disease, which occurs in about 1 out of 100,000 births. A normally-functioning liver takes glucose from the blood stream and stores it as glycogen. This glycogen is then used as an energy source by the body. In GSD-1a, the enzyme microsomal glucose-6 phosphate (G6Phase) that assists the liver in storing the glycogen, is not produced. So the liver has a problem with storing and releasing glycogen. Due to this the sugar levels in the blood drop. If the blood sugar level drops too much, the patient can suffer seizures and organ damage.

Following a special diet can help with maintaining the glucose levels, but in the long run this does not prevent liver damage or rule out the possibility of cancer or kidney failure.

Researchers at Duke University Medical Center have devised a gene therapy technique where the correct genetic code, by way of a harmless virus vector, is inserted into the liver cells to induce them to produce the necessary enzyme.

In experiments conducted on mice and dogs, gene therapy replaced the missing enzyme in the liver to fully normal levels and the patients were protected from low glucose for up to a year.

The problem with gene therapy is that when the liver cells divide and reproduce, the enzyme genes are not transferred with them. They will need to be introduced anew. However, as liver cells divide very slowly, researchers feel that a few shots may suffice over a long period of time.