Patients who suffer from a brutally painful genetic disease called epidermolysis bullosa, which causes blistering skin and open wounds, could benefit from a first-of-its-kind skin-based gene therapy highlighted this week in the Journal of the American Medical Association.
Four patients in an early-stage clinical trial at Stanford University received skin grafts to cover their open wounds, some of which hadn’t healed for five years. The skin grafts had been genetically “corrected” to express the type-7 collagen protein that people with the disease lack the ability to produce. So instead of instantly blistering skin because of loose connections between the upper and lower layers, the collagen helps anchor the skin to itself, allowing it to heal.
To create the skin, the researchers introduced the type-7 collagen gene into batches of a patient’s skin via a viral vector and grew them into sheets about four or five inches long. In almost all cases, the protein could be found in the correct location after three months, and in almost half the cases, it could be found after a year.
The trial showed that the treatment is safe and that some of the long-term wounds had begun to heal. It's the first time a skin-based gene therapy demonstrated both safety and efficacy.
But this early test was conducted with adult patients, and in its most serious forms epidermolysis bullosa can be fatal to infants, while in less severe cases patients live to their teens or early adulthood with constant care. So the researchers are looking to begin a new trial with patients as young as 13 to address the ages most affected by the disease. Many patients ultimately succumb to squamous cell carcinoma as teens or young adults.
"Moving into the pediatric population may allow us to intervene before serious chronic wounds and scars appear,” researcher Peter Marinkovich, who shared authorship with Jean Tang and Zurab Siprashvili, said in a release. “…Since the time of my research training in the laboratory of Robert Burgeson, who discovered type-7 collagen, I've been deeply motivated to contribute to the EB community, and it is very satisfying to be able to finally see this molecular therapy come to fruition."