Transgenic stem cells lead to a miraculous cure

Sometimes I read a science paper and I just say "Holy cow, this is amazing." I don't have that reaction very often, but I did last week.

Amidst all the hype, the hope, and the controversy about gene therapy and stem cell research, some very real progress is being made. Scientists can create working versions of human genes, package them into a virus, and then use the virus to deliver the genes to a real person. This approach creates "transgenic" cells that have bits of virus DNA within them, but the virus can be engineered to be harmless.

Last week, scientists reported in the journal Nature how they saved the life of a 7-year-old boy using transgenic stem cells. Twenty years ago, this would have been science fiction. Even today it is nothing short of astonishing.

Here's the story, summarized from the paper by Tobias Hirsch, Michele de Luca, and their colleagues. In June 2015, a 7-year-old boy was admitted to the Burn Unit of Children’s Hospital of Ruhr University, in Bochum, Germany, where Hirsch and his colleagues (Tobias Rothoeft, Norbert Teig, and others) work. The child wasn't suffering from burns: he had a devastating genetic disease, junctional epidermolysis bullosa (JEB), that had caused him to lose 80% of his skin.

Figure 1b from Hirsch et al. Schematic
representation of the clinical picture.
The denuded skin is indicated in red;
blistering areas are indicated in green.
Flesh-colored areas indicate currently
non- blistering skin. Transgenic grafts
were applied on both red and green areas.

Children with JEB suffer from constant blistering, wounds, and scarring. The disease is uncurable and children often die before reaching their teens. The 7-year-old boy was near death when he was admitted to the hospital–his weight had dropped to 17 kilograms (38 pounds) and he had severe skin infections from streptococcus and pseudomonas bacteria.

Dr. Hirsch and his team were struggling to keep the boy alive, and they had no treatments to offer. In desperation, they searched the scientific literature and found a possible treatment using gene therapy, developed by Michele De Luca, of the Center for Regenerative Medicine at the University of Modena and Reggio Emilia in Italy. Dr. De Luca had only tried this treatment twice before, and even then only on tiny patches of skin. He had never tried it on such a severe case.

The boy and his parents had no other options to save his life. They agreed to let Dr. De Luca try.

In September of 2015, De Luca took a small patch of undamaged skin (4 square centimeters) back to his lab in Italy. There, he used a retrovirus containing a functioning copy of the LAMB3 gene–the gene that was mutated in the boy–to infect the skin cells. The retrovirus integrated itself into the genome of many of the skin cells, giving them the ability to function normally. Then De Luca grew the repaired cells into new skin grafts, enough to cover 80% of the child's body.

In a series of surgeries starting in October 2015, Hirsch and his colleagues applied the skin grafts to the young boy. The results were amazing.

As reported in the paper itself:

"Virtually complete epidermal regeneration was observed after 1 month.... Over the following weeks, the regenerated epidermis surrounding the open lesions and the epidermal islands spread and covered most of the denuded areas."

In other words, it worked. The new skin completely replaced the missing or damaged skin on 80% of the boy's body. What's even more remarkable is that two years later, his skin remains normal. The new skin is functioning perfectly and the young boy has returned to school.

The science behind this treatment represents the culmination of decades of research into gene therapy, stem cells, retroviruses, and genomics. To make it all work, we had to know: the identity of the gene that caused the disease (LAMB3); the DNA sequence of a normal LAMB3 gene; how to insert the human gene into a retrovirus; how to create a modified retrovirus that wouldn't harm humans; and much more.

The success of the therapy also revealed new insights into stem cells in human skin: the small patch of undamaged skin from the boy contained many cells, a few of which were stem cells (holoclones) that could replenish the skin indefinitely. It was these stem cells that allowed the skin grafts to take hold and continue to function, hopefully for the rest of the boy's life.

Sometimes science and medicine converge, and miracles happen.

(Note: the paper is "Regeneration of the entire human epidermis using transgenic stem cells" by T. Hirsch et al.)