Gene therapy

The first person to receive gene therapy in 1990 for SCID was a girl named Ashanti De Silva, who is now a healthy adolescent. Although the gene therapy seems to have worked in saving her life, she and the others who were part of the initial trials also receive injections of the ADA enzyme encoded by the therapeutic gene. There continues to be debate as to whether success in such cases is from gene therapy or the enzyme treatments - or both.i

In 2000, a group of French researchers were able to successfully alter hemopoietic stem cells (ancestor cells of all new blood cells) in a group of babies with SCID.ii Because all new white blood cells produced in these children have the therapeutic gene, they required no additional enzyme treatments. This treatment appeared very successful, restoring immune function to most of the children who received it. Although this "cure" was a milestone in gene therapy it was later discovered that three of the children using this method of gene therapy later developed a leukaemia-like disorder. Two of the children died. Researchers found that the leukemia occurred because the newly transferred gamma c gene had stitched itself into the wrong place, interrupting the function of a gene that normally helps regulate the rate at which cells divide. As a result, the cells began to divide out of control, causing the blood cancer leukemia. Not surprisingly, this was a tragic setback to the progress in gene therapy.

Targeting a gene to the correct cells is crucial to the success of any gene therapy treatment. Just as important, though , is making sure that the gene is not incorporated into the wrong cells.

Another tragic setback for gene therapy was the unexpected death of 18 year old Jesse Gelsinger in 1999. Jesse's genetic liver disorder was being treated successfully with diet and medication. However, Jesse wanted to help others with his condition, so he entered a gene therapy trial at the University of Pennsylvania.iii Tragically, a hyperimmune reaction to the virus used to transfer the therapeutic gene caused multiple organ failure - his death halted all discussion on how best to regulate experimental trials and report health problems in volunteer patients. Our immune systems are very good at fighting off intruders such as bacteria viruses and other biological substances. Gene delivery vectors must be able to escape the body's natural surveillance systems. Failure to do so can cause serious illness and in Jesse's case - death.

A German and Swiss collaboration have successfully treated patients with chronic granulomatous disease (CGD), an immune deficiency, by removing bone marrow-derived stem cells from the patients, inserting the working copy of the target gene, and then replacing the modified cells. The modified stem cells multiplied successfully and the patients started producing NADPH oxidase. One of the two patients is even able to stop taking preventable antibiotics.iv This is an encouraging success.

Despite setbacks and concerns, there are currently hundreds of ongoing gene therapy trials for diverse genetic disorders, cancer, and even aging. There are huge hurdles to overcome before we see widespread success of gene therapies - not to mention the high costs and risks involved. There may come a time when many genetic diseases are routinely treated - or even cured - with success of gene therapy.

References

i http://www.ich.ucl.ac.uk/pressoffice/pressrelease_00592

ii http://evolve.elsevier.com/staticPages/s_login.html

iii http://www.gene.ch/gentech/1999/Dec/msg00005.html

iv http://arstechnica.com/articles/columns/science/science-20050611.ars

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