Is Gene Therapy the Way to Go?

Today my wife and I found out that our HLA is only a 50% match with our son. For those of you who are unaware of what HLA is, I will explain. HLA cells are located in all of you organs and tissue in your body. They let your body know what belongs to you and what is foreign (like a virus). There are many locations where HLA reside but there are only really 6 that are extremely important in making sure that your immune system identifies what is yours and what is not. The chances of you having the exact same combination of HLA as someone else in the world at those spots is extremely slim.

That said, when two people produce a baby they supply the child with half of their HLA typing. Just as you are responsible for giving half of the rest of your genes to your child, you and your spouse do the same for HLA. That means Parker got half of his HLA from me and half from his mother. So at the very least, he would be a 50% match with us. The chances of him being any more of a match than that would require there being some strange similarities in my wife and my genetic makeup if you know what I mean (kissing cousins ... hint hint).

Now, why is HLA important? Well, if Parker is getting stem cells from us that would mean that we would not be identical matches. The only way he would have an identical match would for him to have a sibling that got the same HLA from us. When a stem cell transplant is done with parents it is usually the same situation that we are in (3 out of 6) and is called a Haploidentical Stem Cell Transplant. Sick Kids in Toronto has been successful with this type of treatment; however, it has been unsuccessful more often than not. That said, many of the children were far worse off than Parker, as they had already caught several infections. This presentation by the FDA explains the different treatments that have been done for patients with SCID-ADA and how successful they have been.

The first gene therapy trial ever done was with ADA. The reason being is that SCID-ADA is caused by a single gene, it is easy to regulate as it is always turned on in our bodies, and finally the ADA gene only needs to work at a 10% level to be very successful. The main centers that perform gene therapy are Italy, UK, France, U.S., and Japan. Gene therapy has come a long way since its first use in 1991. The protocol has changes several times.

Currently, Italy has been the most successful with gene therapy. They were the first center to attempt gene therapy and have currently done seven human clinical trials in the past five years with their newest protocol. All of which have been successful to some degree. We have currently been told that the center in Italy would accept Parker in their clinical trials. In the following paragraph I will explain the current protocol for gene therapy as performed by the center in Italy.

The procedure begins by removing stem cells from the patient. These cells are then placed in a culture and infected with a retrovirus that has been encoded with ADA. The patient is conditioned with a medication called busulfan (a mild form of chemotherapy: non-myeloablative conditioning) at a relatively low dose to make space in the bone marrow for the growth of new working stem cells. Once the patient is conditioned, the retovirus with the improved stems cells are reinfused into the blood stream. The retrovirus binds to the cell and allows the RNA to create a small piece of corrected DNA that gets inserted into the patients own DNA. When this occurs we have cells in the body that have a working ADA gene in them. Check out this site for a more illustrated version of what happens at the cellular level. Check other then viruses as vectors and work from their.

Many of you may have read or heard about the deaths in France that occured due to children who obtained leukemia as a result of gene therapy. The reason was that the DNA binded to the incorrect spot in the DNA. The trial consisted of 18 patients. Of those, three contracted leukemia, one of those died. As a result, the gene therapy for SCID patients was discontinued in the United States.

It is to be noted that the trials in France did not deal with SCID-ADA but X-Linked SCID. As a result, the ban on SCID-ADA gene therapy has been lifted in the United States as it follows the same successful protocol developed in Milan, Italy.