Stanford team is growing healthy skin for diseased patients – The Mercury News
By daniellenierenberg
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Small sheets of healthy skin are being grown from scratch at a Stanford University lab, proof that gene therapy can help heal a rare disease that causes great human suffering.
The precious skin represents growing hope for patients who suffer from the incurable blistering disease epidermolysis bullosa and acceleration of the once-beleaguered field of gene therapy, which strives to cure disease by inserting missing genes into sick cells.
It is pink and healthy. Its tougher. It doesnt blister, said patient and research volunteer Monique Roeder, 33, of Cedar City, Utah, who has received grafts of corrected skin cells, each about the size of an iPhone 5, to cover wounds on her arms.
More than 10,000 human diseases are caused by a single gene defect, and epidermolysis bullosa is among the most devastating. Patients lack a critical protein that binds the layers of skin together. Without this protein, the skin tears apart, causing severe pain, infection, disfigurement and in many cases, early death from an aggressive form of skin cancer.
The corrected skin is part of a pipeline of potential gene therapies at Stanfords new Center for Definitive and Curative Medicine, announced last week.
The center, a new joint initiative of Stanford Healthcare, Stanford Childrens Health, and the Stanford School of Medicine, is designed to accelerate cellular therapies at the universitys state-of-the-art manufacturing facility on Palo Altos California Avenue. Simultaneously, itisaiming to bring cures to patients faster than before and boost the financial value of Stanfords discoveries before theyre licensed out to biotech companies.
With trials such as these, we are entering a new era in medicine, said Dr. Lloyd B. Minor, dean of the Stanford University School of Medicine.
Gene therapy was dealt a major setback in 1999 when Jesse Gelsinger, an Arizona teenager with a genetic liver disease, had a fatal reaction to the virus that scientists had used to insert a corrective gene.
But current trials are safer, more precise and build on better basic understanding. Stanford is also using gene therapy to target other diseases, such as sickle cell anemia and beta thalassemia,a blood disorder that reduces the production of hemoglobin.
There are several diseases that are miserable and worthy of gene therapy approaches, said associate professor of dermatology Dr. Jean Tang, who co-led the trial with Dr. Peter Marinkovich. But epidermolysis bullosa, she said, is one of the worst of the worst.
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It took nearly 20 years for Stanford researchers to bring this gene therapy to Roeder and her fellow patients.
It is very satisfying to be able to finally give patients something that can help them, said Marinkovich.In some cases, wounds that had not healed for five years were successfully healed with the gene therapy.
Before, he noted, there was only limited amounts of what you can do for them. We can treat their wounds and give them sophisticated Band-Aids. But after you give them all that stuff, you still see the skin falling apart, Marinkovich said. This makes you feel like youre making a difference in the world.
Roeder seemed healthy at birth. But when her family celebrated her arrival by imprinting her tiny feet on a keepsake birth certificate, she blistered. They encouraged her to lead a normal childhood, riding bicycles and gentle horses. Shes happily married. But shes grown cautious, focusing on photography, writing a blog and enjoying her pets.
Scarring has caused her hands and feet digits to become mittened or webbed. Due to pain and risk of injury, she uses a wheelchair rather than walking long distances.
Every movement has to be planned out in my head so I dont upset my skin somehow, she said. Wound care can take three to six hours a day.
She heard about the Stanford research shortly after losing her best friend, who also had epidermolysis bullosa, to skin cancer, a common consequence of the disease. Roeder thought: Why dont you try? She didnt get the chance.
The team of Stanford experts harvested a small sample of skin cells, about the size of a pencil eraser, from her back. They put her cells in warm broth in a petri dish, where they thrived.
To this broth they added a special virus, carrying the missing gene. Once infected, the cells began producing normal collagen.
They coaxed these genetically corrected cells to form sheets of skin. The sheets were then surgically grafted onto a patients chronic or new wounds in six locations. The team reported their initial results in Novembers Journal of the American Medical Association.
Historically, medical treatment has had limited options: excising a sick organ or giving medicine, said Dr. Anthony E. Oro of Stanfords Institute for Stem Cell Biology and Regenerative Medicine. When those two arent possible, theres only symptom relief.
But the deciphering of the human genome, and new tools in gene repair, have changed the therapeutic landscape.
Now that we know the genetic basis of disease, we can use the confluence of stem cell biology, genome editing and tissue engineering to develop therapies, Oro said.
Its not practical to wrap the entire body of a patient with epidermolysis bullosa in vast sheets of new skin, like a mummy, Oro said.
But now that the team has proved that gene therapy works, they can try related approaches, such as using gene-editing tools directly on the patients skin, or applying corrected cells like a spray-on tan.
A cure doesnt take one step, said Tang. It takes many steps towards disease modification, and this is the first big one. Were always looking for something better.
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Stanford team is growing healthy skin for diseased patients - The Mercury News
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