How a tiny patch of skin helped researchers save the life of a young boy battling a deadly disease

 

EB boy

After receiving his new skin, the boy plays on the grounds of the hospital in Bochum, Germany. Credit: RUB

By any standards epidermolysis bullosa (EB) is a nasty disease. It’s a genetic condition that causes the skin to blister, break and tear off. At best, it’s painful and disfiguring. At worst, it can be fatal. Now researchers in Italy have come up with an approach that could offer hope for people battling the condition.

EB is caused by genetic mutations that leave the top layer of skin unable to anchor to inner layers. People born with EB are often called “Butterfly Children” because, as the analogy goes, their skin is as fragile as the wings of a butterfly. There are no cures and the only treatment involves constantly dressing the skin, sometimes several times a day. With each change of dressing, layers of skin can be peeled away, causing pain.

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Hands of a person with EB

Life and death for one boy

For Hassan, a seven-year old boy admitted to the Burn Unit of the Children’s Hospital in Bochum, Germany, the condition was particularly severe. Since birth Hassan had repeatedly developed blisters all over his body, but several weeks before being admitted to the hospital his condition took an even more serious turn. He had lost skin on around 80 percent of his body and he was battling severe infections. His life hung in the balance.

Hassan’s form of EB was caused by a mutation in a single gene, called LAMB3. Fortunately, a team of researchers at the University of Modena and Reggio Emilia in Italy had been doing work in this area and had a potential treatment.

To repair the damage the researchers took a leaf out of the way severe burns are treated, using layers of skin to replace the damaged surface. In this case the team took a tiny piece of skin, about half an inch square, from Hassan and, in the laboratory, used a retrovirus to deliver a corrected version of the defective gene into the skin cells.

 

They then used the stem cells in the skin to grow sizable sheets of new skin, ranging in size from about 20 to 60 square inches, and used that to replace the damaged skin.

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In the study, published in the journal Nature, the researchers say the technique worked quickly:

“Upon removal of the non-adhering gauze (ten days after grafting) epidermal engraftment was evident. One month after grafting, epidermal regeneration was stable and complete. Thus approximately 80% of the patient’s TBSA (total body surface area) was restored by the transgenic epidermis.”

The engrafted skin not only covered all the damaged areas, it also proved remarkably durable. In the two years since the surgery the skin has remained, in the words of the researchers, “stable and robust, and does not blister, itch, or require ointment or medications.”

In an interview in Science, Jakub Tolar, an expert on EB at the University of Minnesota, talked about the significance of this study:

“It is very unusual that we would see a publication with a single case study anymore, but this one is a little different. This is one of these [studies] that can determine where the future of the field is going to go.”

Because the treatment focused on one particular genetic mutation it won’t be a cure for all EB patients, but it could provide vital information to help many people with the disease. The researchers identified a particular category of cells that seemed to play a key role in helping repair the skin. These cells, called holoclones, could be an important target for future research.

The researchers also said that if a child is diagnosed with EB at birth then skin cells can be taken and turned into a ready-made supply of the sheets that can be used to treat skin lesions when they develop. This would enable doctors to treat problems before they become serious, rather than have to try and repair the damage later.

As for Hassan, he is now back in school, leading a normal life and is even able to play soccer.

 

 

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Scientists Develop Stem Cell ‘Special Forces’ in order to Target, Destroy Brain Tumors

Curing someone of cancer is, in theory, a piece of cake: all you have to do is kill the cancer cells while leaving the healthy cells intact.

But in practice, this solution is far more difficult. In fact, it remains one of the great unsolved problems in modern oncology: how do you find, target and destroy each individual cancer cell in the body—while minimizing damage to the surrounding cells.

Encapsulated toxin-producing stem cells (in blue) help kill brain tumor cells in the tumor resection cavity (in green). [Credit: Khalid Shah, MS, PhD]

Encapsulated toxin-producing stem cells (in blue) help kill brain tumor cells in the tumor resection cavity (in green). [Credit: Khalid Shah, MS, PhD]

But luckily, Harvard Stem Cell Institute scientists at Massachusetts General Hospital may have finally struck gold: they have designed special, toxin-secreting stem cells that can target and destroy brain tumors. Their findings, which were performed in laboratory mice and which appear in the latest issue of the journal STEM CELLS, offer up an entirely unique method for eradicating deadly cancers.

Harvard Neuroscientist Khalid Shah, who led the study, explained in last Friday’s news release that the idea of engineering stem cells to kill cancer cells is not new—but there was a key difference in scientists’ ability to target individual cells vs. difficult-to-reach tumors, which is often the case with brain cancer:

“Cancer-killing toxins have been used with great success in a variety of blood cancers, but they don’t work as well in solid tumors because the cancers aren’t as accessible and the toxins have a short half-life.”

The solution, Shah and his team argued, was stem cells. Previously, Shah and his team discovered that stem cells could be used to circumvent these problems. The fact that stem cells continuously renew meant that they could also be used to continually deliver toxins to brain tumors.

“But first, we needed to genetically engineer stem cells that could resist being killed themselves by the toxins,” said Shah.

In this study, the research team introduced a small genetic change, or mutation, into the stem cells so that they become impervious to the toxin’s harmful effects. They then introduced a second mutation that allowed the stem cells to maintain and produce and secrete toxins throughout the cells’ lifetime—effectively giving it an unlimited supply of ammunition to use once it encountered the brain tumor.

They then employed a common technique whereby the toxins were tagged so that they only sought out and infected cancer cells—leaving healthy cells unscathed.

“We tested these stem cells in a clinically relevant mouse model of brain cancer,” Shah described. “After doing all of the molecular analysis and imaging to track the inhibition of protein synthesis within brain tumors, we do see the toxins kill the cancer cells and eventually prolonging the survival in animal models.”

While preliminary, these results are encouraging. As the team continues to refine their method of development and delivery, they are optimistic that they can bring their methods to clinical trial within the next five years.