Overview

A new treatment for severe dystrophic epidermolysis bullosa (EB), a rare and painful genetic skin condition, has received approval from the U.S. Food and Drug Administration (FDA). This treatment, developed by researchers at Stanford Medicine, utilizes genetically engineered skin grafts derived from patients' own cells to effectively heal chronic wounds associated with the disorder.

Understanding Dystrophic Epidermolysis Bullosa

Dystrophic epidermolysis bullosa is an extremely rare condition, affecting approximately 1 in 500,000 individuals. The disorder is caused by mutations in the gene responsible for collagen VII, a protein integral to skin integrity. In individuals with EB, this absence of functional collagen VII leads to an extreme fragility of the skin, causing it to blister and form wounds at the slightest touch. These wounds can remain unhealed for extended periods, leading to severe discomfort and a higher risk of infections and skin cancer.

Research Journey to Treatment Approval

The journey toward developing this skin graft therapy began in 2003 when a team of researchers at Stanford, led by Dr. Paul Khavari, discovered a method to genetically modify skin cells from EB patients to correct the defect in collagen VII. Initial studies demonstrated that these modified cells could be cultivated into functional skin sheets and safely grafted onto mice.

Over the following two decades, this foundational research evolved through multiple clinical trials, culminating in a Phase 1 study that demonstrated the safety and potential effectiveness of the gene therapy skin grafts. This pivotal work was a collaborative effort involving several dermatology experts at Stanford, who have now paved the way for the clinical application of this innovative treatment.

Mechanism of the Skin Grafts

To create the skin grafts, a physician first obtains a small biopsy from the patient's unaffected skin. In the laboratory, this biopsy is treated with a retrovirus to introduce a corrected version of the collagen VII gene. The engineered cells are then cultured into sheets of skin, which typically measure about the size of a credit card. The entire process takes approximately 25 days, after which the grafts can be sutured onto the patient's wounds in a hospital setting.

Patients can expect a hospital stay of about one week for recovery. As these grafts utilize the patient's own cells, there is minimal risk of immune rejection, making the treatment both safe and effective.

Impact of the Treatment on Patients

Feedback from participants in the clinical trials has been overwhelmingly positive, highlighting the significant improvement in quality of life following the application of these grafts. Many patients reported a substantial reduction in the pain and management associated with chronic wounds, allowing them to engage in daily activities and attend school more freely. The hope is that with early intervention using this therapy, the progression of EB can be effectively mitigated, reducing the severity of symptoms and enhancing patient well-being.

Future Directions

With the FDA's approval, the skin grafts will soon be available at five hospitals across the United States, including Lucile Packard Children's Hospital at Stanford. The ongoing research aims to further refine these treatments and explore additional therapeutic options that could further alleviate the burden of dystrophic epidermolysis bullosa.