RDEB is a congenital, progressive, devastatingly painful and debilitating genetic disorder that often leads to death, and is the most severe form of dystrophic epidermolysis bullosa2. RDEB causes severe blistering and areas of missing skin, which is a response to any kind of friction, including normal daily occurrences like rubbing or scratching. Children who inherit the condition are often called “butterfly children” because their skin is as fragile as a butterfly’s wings.
RDEB patients do not produce functional Type VII collagen (COL7) due to a mutation in the COL7A1 gene. Collagen 7—a protein—is the main component of anchoring fibrils that hold together the layers of skin. Without these fibrils, skin layers separate causing severe blistering, open wounds and scarring in response to any kind of friction or trauma.
Genetic disorders occur when a copy (or copies) of a defective gene is transmitted from parent to child. RDEB is an autosomal recessive disorder, meaning that a child has inherited copies of the defective gene from both parents. In the case of RDEB, a child receives a recessive gene from both parents.
There are approximately 1,100 – 2,500 patients in the United States suffering from RDEB. Presently, there is no cure for this orphan disease. RDEB patients have the highest rate of morbidity and mortality of all genetic blistering disorders. It affects both genders and every racial and ethnic background equally.
Current treatments for RDEB—including daily bandaging, antibiotics, feeding tubes, and hand and esophageal surgeries—address only the symptoms.
Fibrocell’s FCX-007 is an autologous dermal fibroblast genetically modified to express functional COL7 that is missing or deficient in these patients. Transduced with a lentiviral vector containing the COL7 producing gene, known as COL7A1, FCX-007 is injected directly into the papillary dermis of blisters and wounds where the protein enables formation of anchoring fibrils to hold the layers of skin together. FCX-007 offers the potential to address the underlying cause of RDEB by providing high levels of COL7 directly to the affected areas, thereby avoiding systemic treatment.
The U. S. Food and Drug Administration (FDA) has granted Orphan Designation to FCX-007 for the treatment of Dystrophic Epidermolysis Bullosa, which includes RDEB. In addition, FCX-007 has been granted Rare Pediatric Disease Designation and Fast Track Designation by the FDA for treatment of RDEB.
Fibrocell is developing FCX-007 in collaboration with Intrexon Corporation, a leader in synthetic biology.
Dermal fibroblasts are collected from the patient, cultured and genetically modified to provide high levels of COL7 and then injected locally into the affected areas.
Photo left: Courtesy of EB Research Partnership and the Hall family.and the Hall Family. Credit: Hal Horowitz.
Photo right: Courtesy of debra–The Dystrophic Epidermolysis Bullosa Research Association of America. Used with permission.