Nate Liao lives with constant, painful blistering skin. He and his 5-year-old brother, Jake, have the worst form of a genetic skin disease called epidermolysis bullosa (EB).

"If you can imagine the worst blister you may get on your foot -- multiply that by a thousand," said Theresa Liao.

Liao and her husband Roger both carry the gene for EB. For two of their four sons, it means enduring years of painful wounds that lead to an aggressive skin cancer.

There is no treatment. Liao can only bandage the boys from head to toe. Already, Jake's fingers have fused together from repeated scarring and he's lost all his toes.

"He had such severe problems with hands when he was born, you could literally blow on them and the skin would separate," Liao said.

She researched the disease and the possibility of a cure using stem cells. Doctors at the University of Minnesota studied lab mice with EB. The mice, like the brothers, lack a protein that keeps skin together.

"It works like a Velcro. It works like having tiny fibrils, many of them that will keep the layers together and if they are not kept together, then the blisters develop," said Dr. Jakub Tolar, a bone marrow transplant doctor with the University of Minnesota.

Doctors infused healthy stem cells -- by way of bone marrow transplants -- into the sick mice. And the blisters disappeared. After that success in the lab, Nate became the first human to receive a bone marrow transplant to treat EB. His healthy 3-year-old brother, Jullian, was the donor.

"You have to know that your child could die. But I know my child could die anyway and this was a chance to make it better," Liao said.

It will be several more weeks before doctors know if the stem cell treatment worked, but Liao thinks Nate has shown some improvement. Whether or not it works for the Liao family, doctors believe this could help people with a variety of skin diseases.

Extended Interview With Dr. Jakub Tolar

What is epidermolysis bullosa?

Dr. Tolar: It is an incurable disease and presents lifelong blistering of the skin. It is very painful, and never goes away. It ultimately irritates the skin to the point that cancers develop. When they do develop, everybody who has this disease will die of these cancers before they reach young adulthood.

How do you get the disease?

Dr. Tolar: It’s a genetic disease. We all have a gene in our system that is supposed to make the protein that is faulty in this gene. The protein is called collagen seven. It’s a protein that is found mainly in the skin. Most people have it which is why they don’t have the disease. Some very infrequent people have a mistake in the DNA, in the template for this protein that can be passed to them from their parents. You have two copies of each gene, one from our mother and one from the father and if both of these copies of the gene are with a mistake then the child will have the disease.

Are there varying degrees of the disease -- what are the symptoms?

Dr. Tolar: There are other forms that are not lethal, but all of them have a mistake in this gene that makes the skin not adhere. That means blisters develop as a result of the layers of the skin not adhering to each other. The role of the Collagen 7 protein is to keep these layers together. It works like Velcro -- having many tiny fibers that keep the layers together. If they are not kept together then blisters develop. There are two main layers of skin -- one on the top, the one that we see, and one on the bottom that we don’t see that feeds the cells in the top layer. Even though there are four or more layers in the top one and many layers in the bottom one, the top and bottom layers both function as a unit. They need to be kept together to function.

Where do blisters develop?

Dr. Tolar: Blisters can develop anywhere on the skin or they can also develop on the mucosa lining of the mouth, of the esophageus. They are very difficult to manage with any treatment because they are in the way of feeding the child. They can also trigger the growth of cancers in spots like mouth or esophageus.

What level of injury does it take for blistering to occur?

Dr. Tolar: Very little, even a minor injury that you would not even consider an injury. Really, pressure on the skin will result in these two layers separating and then body fluids will get into it the space and fill it.

Is the blistering painful?

Dr. Tolar: Yes, it’s very painful. The stories of these children are horrible. Their whole life revolves around these ongoing painful blisters which are as painful as a burn. Imagine that these children have an ongoing burn on their skin that will never heal.

How many kids are born with epidermolysis bullosa?

Dr. Tolar: Several hundred in the United States.

How was Nate brought to your attention?

Dr. Tolar: My boss, Dr. John Wagner was traveling and giving lectures and he was approached by Theresa, Nate’s mother. She asked him to help Nate. Dr. Wagner came back here and talked to Dr. Bruce Blazer who is the head of the division of the bone marrow transplant here. Dr. Blazer and I talked and felt we should design a way to treat these children.

How did you find a new the treatment for epidermolysis bullosa?

Dr. Tolar: We genetically engineered mice to have the same disease and then we planned all the possible strategies that could be helpful. We started from the source of the cells taken from the bone marrow. The reason for that is at least two-fold. The first is we have a 50 year history of bone marrow transplantation to show we can actually transfer cells from one individual to another and recreate the whole lymphoid system and blood forming system in the body. So we know how to do it. The second reason is that all the cells from the donor should be able to make collagen 7. The trick is, we didn’t know which ones, and we didn’t know whether the cells, even if they had the right gene for this protein, would actually express it.

How did the bone marrow transplant work in the mice?

Dr. Tolar: We took different types of cells from the bone marrow and we tested them one by one. There were about 16 of them and 15 didn’t work. The one that we identified actually worked in about one quarter of the animals tested. Mice that are typically not able to live beyond two weeks survived. This was extremely exciting because it was totally new and never happened before. We didn’t know at that time if this was because we had taken cells from the healthy mouse and put it into the mouse with the disease, like the situation in our bone marrow transplant practice where we take the cells from a healthy donor and put it in a child with the disease. What we needed to show and what we did show, was that cells from healthy mice traveled into the skin of diseased mice and expressed the collagen 7 protein. We have special stain to show us that the protein is actually there. We were also able to show that the diseased mice formed Velcro-like fibers, called anchoring fibers, that anchor the top layer of the skin to the bottom layer of the skin to keep it healthy.

How successful was your study in mice?

Dr. Tolar: It was a partial success. Not every single mouse treated with this population actually survived and had successful results. This is what happens in medicine and science -- there is nothing that is 100 percent. Everything is graded, everything is a chance occurrence in many ways. Even though this was not a complete recovery, it was a first sign and it was a first proof that this principle was actually possible.

When did you approach Nate and his mother with your findings?

Dr. Tolar: We had this mother that is incredibly motivated because two of her children have a lethal disease. We were prodded by her and by funding we have received from children’s research cancer fund and other places to actually do something with this. Once we had some foundation from the laboratory to show that this is a possibility and is a good biologic approach, we went to Nate to give him the transplant from his brother.

So you took the bone marrow for Nate’s transplant from his healthy brother?

Dr. Tolar: That is exactly what we did. So we took the healthy cells from the healthier brother and gave them to Nate.

When did Nate's transplant occur?

Dr. Tolar: About 100 days ago. Very importantly, there is nothing that I can say with any definitive truth at the moment because it’s too early. All I can say is that this he is apparently healthy at the moment, from the standpoint of surviving the transplantation itself. He still has blisters and we are currently looking at whether the collagen 7 has been made.

If the transplant is successful, what will it mean for other kids?

Dr. Tolar: Very interesting. First, let’s start with a kid that had the same disease. If this were successful, it would offer a tremendous opportunity to the other children with epidermolysis bullosa. The second important thing is that there are many other skin diseases that are not being treated at all. The skin has other proteins than collagen 7, and in theory these same cells should be able to make these proteins as well.

Is there anything else you want to add?

Dr. Tolar: I want to add that this would not have been possible without several building blocks in the mix. One is that there is a group of very smart people -- a critical mass of intelligent people here at the University of Minnesota that makes this possible. Nobody is smart enough on his or her own. You really need other people to help make an idea, transfer it from just an idea to something that can translate into the clinic. The second important thing is that there is an understanding of funding and structure of the whole university, especially in our division of bone marrow transplant, that you need people to go to the laboratory and prove that a treatment works in animals before it is brought to the clinic. Third is that the community here in Minnesota or funding agents at the federal level understand it costs a lot money and their support allows us to do research.

Additional Information About EB

Epidermolysis bullosa (EB) is a rare genetic disease characterized by incredibly fragile skin tissue and recurrent blister formation from minor friction or trauma.

The severity of the condition varies depending on the form (Simplex EB, Junctional EB, Recessive Dystrophic, or Dominant Dystrophic).

The latest figures from the national EB registry find the condition affects less than 10,000 children and adults in the United States. It occurs in all racial groups and genders in equal numbers.

Infancy is an especially difficult time for patients with EB. Blistering can be caused by the slightest touch of skin, clothing or, in severe cases, air. The blisters can lead to infection, sepsis and even death. Severe forms of EB increase the risk of mortality during infancy -- patients with the Herlitz or Letalis form of juvenile EB have the highest risk of 87 percent during the first year of life.

Patients with EB lack anchors that hold the layers of skin together. Any activity that rubs or causes pressure to the skin results in painful sores and blisters. Even bathing these children is difficult because water touching the open wounds causes incredible pain and washing the skin can lead to further blistering.

Many patients must live on a liquid diet or eat only soft foods because the esophagus can also blister. Over time, repeated healing and scarring on the hands and feet can cause the tissue to form stumps where the tissue has overgrown the digits. The condition can also lead to squamous cell carcinoma -- an aggressive skin cancer.

Many parents find bandaging children with gauze and ointment from head to toe can prevent skin damage. However, damage can still occur beneath these bandages because pressure can also lead to the painful wounds. While ointments and skin grafts have shown some success and are being tested to see if they will help treat the disease, there is no known cure or treatment for EB.

New stem cell therapy is being tested at the University of Minnesota by way of bone marrow transplants from healthy people who are matches to patients with EB. A 100-day trial is currently underway in Minnesota to find out if the treatment worked for a young boy with the disease. Results are not yet available, but both doctors and the boy's family are hopeful and feel they have seen some progress so far.

The genes that cause EB can be either dominant or recessive. The dominant forms (Simplex and Dominant Dystrophic) are caused when a parent is a carrier of the dominant gene. A dominant carrier parent has a 50 percent chance of transmitting the abnormal gene with each pregnancy.

Rarely, children can be born with a genetic mutation that causes the disease when neither parent is a carrier. The affected child will also have a 50 percent chance of passing the disease to his or her children.

Junctional and Recessive Dystrophic EB conditions are caused by a recessive gene expression. If both parents are carriers of the unexpressed gene, with each pregnancy, they have a 25 percent chance of the genes expressing themselves in the child, causing EB.

Additional Resource:

• University of Minnesota Pediatrics