Dr. Bortrum
12/01/2017
Gene Therapy in Children
CHAPTER 87 Saving Young Lives
There's a boy in Germany who is in school and playing soccer. Nothing special about that, you say? Yes, there is. Two years ago this child was near death. In our New Jersey newspaper The Star-Ledger of November 9, I found an article by Maria Cheng of Associated Press with the bold headline "Boy with rare disease gets a new skin". The article is about this boy, who was 7 years old back in 2015 suffering from a horrible skin disease known as junctional epidermolysis bullosa (JEB), in which certain gene mutations result in a situation where the outer layer of skin, the epidermis, lacks the proteins that anchor the outer layer tightly to the tissue underneath. The outer skin sloughs off, leaving the child with open sores and blistering of the skin. In 2015, the child had lost 60 percent of his outer skin and was in such pain that the doctors put him into an induced coma to spare him the suffering. Attempts to grow or transplant skin from his father to cover his body were unsuccessful.
Well, the German doctors got in touch with Dr. Michele De Luca and his colleagues at the University of Modena in Italy. They had previously been able to grow a small piece of skin in a similar case using gene therapy. De Luca thought he had a shot at helping the poor boy but cautioned that he could not guarantee the results in such a serious case and it could be fatal. The parents gave their consent and the doctors removed a small patch of good skin about the size of a postage stamp from the boy. To get more details about what happened next I found the abstract of an article the Italian group published in Nature but couldn't understand the medical terms and found an article by Kelly Servick on the Science magazine Web site.
The patch of skin was from an unblistered area in the boy's groin. The doctors then cultured cells from that patch. The cultured cells include stem cells, which apparently are found in the normal skin. The next step was to infect the stem cells with a retrovirus to which they has attached a normal copy of the gene needed to ensure attachment of the outer layer of skin to the inner layer. The stem cells now had the good gene and from these cultures they grew sheets of skin ranging from 50 to 150 square centimeters in size. (From the newspaper article, I got the impression that they grew a single sheet about 3 feet square but now I assume that was the total area of all the smaller sheets.) They then used those sheets to cover the boy's arms, legs, back and some of his chest. Within a month the grafted skin had started to regenerate and eventually covered 80 percent of his body.
Two years later this boy is now an active young fellow playing all kinds of sports and is a poster child for this kind of gene altering therapy. Of course, the doctors are keeping a close eye on him for any sign of relapse or any skin cancer. Early attempts on gene therapy using retroviruses resulted in kids getting leukemia but so far the German boy has shown no signs of any such problem.
At this point I was about to shift gears and talk about an article in the November 3 issue of Science that discusses how we might search for signs of life on planets outside our solar system. However, when I turned the page and saw the picture of a smiling little girl in the following article in Science I knew I had to write about her story since it meshed perfectly with the above story of the boy with the new skin. She and I share a December birthday; this month she will be 3 and I will be 90.
The article, titled "A Second Chance" by Jocelyn Kaiser, deals with the wrenching case of a couple who had a baby girl born with spinal muscular atrophy type 1 (SMA1). This disease gradually paralyzes babies and rarely do they survive more than 2 years, This particular child died at 15 months. Unexpectedly, the mother found herself pregnant again, facing a 1 in 4 chance that the baby would be born with SMA1. Sadly, the baby daughter was indeed born with SMA1, as revealed by genetic testing, and the parents were resigned to just loving her as long as they could. But, fortunately, they searched the internet and found a clinical trial in Ohio testing a gene therapy approach to SMA1.
The gene therapy involved a one-time infusion into a vein of a virus carrying a particular therapeutic gene. Particularly exciting to the medical profession is the fact that the virus carrying the gene crosses the blood-brain barrier and spreads through the central nervous system. Another new drug of promise for treating SMA1 has to be injected into the spine every four months. Well, obviously the gene therapy has so far worked for our little girl or I wouldn't be writing about it. She does have limitations, not being able to run normally or jump but she can dance and walk quickly and if you could see her picture walking and smiling brightly you couldn't help falling in love with her. While we share our birthdays this month I don't expect to have many more, if any, but I hope she has 90 more happy birthdays to come.
Just this morning, before writing this section of the column, I heard a broadcast on the radio by someone discussing gene therapy and the promising results of various new treatments. One downside of these new treatments is the cost, which are in the hundreds of thousands of dollars. The Science article says gene therapies on the market now command $700,000 or more! I can't imagine anyone having to cope with such a high cost for gene therapy. It certainly raises the question as to how much saving a life is worth. If you're the parents of children such as those discussed here there is no question.
Next column on or about January 1, 2018, hopefully. Happy holidays, whatever your choice.
Allen F. Bortrum
