What is Gene Therapy?

As regular readers know, we’ve enrolled Felix in a research trial for something called gene therapy, to treat the life-threatening disease called ADA-SCID. Gene therapy is a cutting-edge medical therapy still in the experimental phase, though outcomes are looking really good so far. Although it’s terrifying to enroll your child in an experimental therapy, it’s by far his best chance at survival.

We are leaving for California in ten days (!!!), so I thought I’d give a better explanation of gene therapy, from my understanding. (Obviously I am not a doctor; this is just the way I understand it, from the explanations I’ve received.)

To begin, you might need a bit of a better understanding about Felix’s condition.

Felix’s Condition

Felix was born with something called adenosine deanimase (ADA) deficiency. It is a genetic disorder of the immune system caused by abnormalities of a specific gene in the body.

The ADA gene is responsible for producing an enzyme called adenosine deanimase. The absence of this enzyme causes the body to accumulate certain toxic waste products, which kill off certain cells of the immune system called T lymphocytes. (T lymphocytes are a type of white blood cell which are necessary to fight infections caused by bacteria, viruses, and fungi.) Without T lymphocytes, Felix has no immune system, which is called severe combined immune deficiency (SCID). (There are many different kinds of SCID: ADA-deficiency is just one of them.)

If untreated, SCID results in death from infection, usually within the first year of life. There are also various other symptoms associated with ADA deficiency which vary from patient to patient. In Felix’s case, his breathing was impaired so that he needed oxygen support, and his liver was slightly inflamed. Other symptoms may have manifested over time.

Ways to Treat ADA Deficiency

In order to treat ADA deficiency, doctors have been trying to find the best way to replace that missing enzyme.

One way to treat ADA deficiency is to simply inject the patient with the missing enzyme (which is harvested from cows). Felix has been receiving this treatment since he was a month old – he gets two injections a week. It very quickly and dramatically improved his health, so that he was able to come off of oxygen, his liver enzymes went down, and he was eventually able to fight off a virus (CMV) that he acquired in his first weeks of life (and that nearly killed him). He has been fairly well for the last few months, though we’ve had to keep him in strict isolation to prevent any new infections.

The trouble with ADA injections is that its effectiveness slowly wears down over the first few years. Moreover, it is incredibly expensive (we’re talking $200,000 a year, for the rest of his life). It’s also not a perfect solution since it’s not human ADA and it’s not being made by the body. So we are still looking for a long-term solution.

Another way doctors have attempted to cure SCID (including ADA-SCID) is through a bone marrow transplant.

Bone marrow contains “stem cells” which make all of the blood cells in the body, including T lymphocytes. So if the patient had his bone marrow replaced with someone else’s that didn’t have the abnormal gene, he should be able to rebuild an immune system.

This has worked with varying success among many SCID patients. The best results come from a matched sibling donor, but you may remember that Lydia turned out not to be a match.

There are many problems related to bone marrow transplants, though, all of which tend to be more severe in patients with ADA deficiency. The major problem is something called graft-versus-host disease, wherein the donor cells attack the patient’s body.

So researchers came up with an idea that could get around the graft-versus-host problem: use the patient’s own bone marrow!

Gene Therapy

That’s the idea behind gene therapy: a bone marrow transplant using the patient’s own bone marrow stem cells that have been corrected.

If we could insert the normal gene for the missing ADA enzyme into the stem cells which make T lymphocytes, then theoretically these T lymphocytes would no longer be destroyed by the toxic waste products, and the immune system could be restored. That’s gene therapy in a nutshell.

Different forms of gene therapy have been tried in a few different places in the world – Milan, Italy; London, England; and Los Angeles. Felix is enrolled in the most recent trial in Los Angeles. Here’s how it works.

How It Works

First you harvest the patient’s bone marrow.

Felix will be placed asleep under general anesthesia for the bone marrow harvest. Two needles go into the hip bones to remove about half a cupful of bone marrow, some for backup in case anything goes wrong.

The bone marrow cells then get taken to a lab where they will be treated with the normal ADA gene.

To get the ADA gene into the stem cells, they use an altered virus called a vector. In this particular trial, they are using an altered HIV virus, also called a lentivirus. Yes, that’s right: we will be purposely exposing Felix’s bone marrow cells to an altered HIV virus, because they’re so effective at getting into cells. (The virus has been altered so that it cannot reproduce itself and all the HIV genes have been removed.) We will essentially be “infecting” his cells with the corrected gene! (Yes, I get freaked out every time I think about it.)

The bone marrow cells will be grown in the lab for two days. Once the ADA gene is in a cell, it is permanent, and the cell will pass the ADA gene on to all blood cells made from that cell, including the T lymphocytes that need to gene to function properly.

Meanwhile, Felix will get treated with chemo to kill some of the stem cells in his bone marrow, to “make space” for the gene-modified cells he will get back. Fortunately, the type of chemo he will get is some of the least harmful kind, and he will get a much lower dose than most transplant patients. He shouldn’t suffer too many side-effects (no hair-loss, minimal nausea, etc.). It takes a week or two for  the chemo to really wipe out his cells.

If everything goes well, two days later he will have the corrected stem cells infused back into his body. This just works like a normal IV. After that, it’s a matter of waiting for the corrected cells to multiply and take over.

Watching and Waiting After Gene Therapy

We will be in LA for  the span of about a week, if all goes well. Then we hop onto a plan (yes, a regular commercial flight — remember, it takes a week or two for the chemo to take effect) and head back for Ontario, where we will be admitted in the hospital. Felix needs to be closely monitored in hospital for at least a month to watch for infection, since the chemo will have wiped out much of his little immune system.

Once he has some of his white blood cells back, he can hopefully go home. We will then remain in isolation at home for many months (anywhere from 4-12) as we wait for his new immune system to build up.

Our biggest fear in all of this comes from his CMV (cytomegalo virus). It is currently undetectable in his blood stream, but will probably come back at some point after the chemo has wiped out his immune system. It is a very serious virus for immune-suppressed people and could pose a threat to his life. Felix is one of the first patients with CMV to be treated with gene therapy, so no one knows exactly what to expect. The hope is that his immune system will be able to reconstitute itself fast enough and strong enough to beat it, as it has before.

Prayer Request

• Please pray that Felix continues to be in good health until we make it to L.A. (He’s made it this far thanks to your prayers!!). We are traveling by commercial flight, after all!
• Pray that there are no complications in gene therapy, and that it works!
• Pray that through the right medications and a quickly-reconstituted immune system, his CMV stays down and doesn’t damage his organs or put his life in danger

Thanks so much for your support!