First systemic therapy for fatal childhood disease

Children with RDEB lack a protein that anchors skin to the body, resulting in fragile skin that sloughs off with little movement or friction. They suffer painful wounds and must be bandaged at all times to protect their skin from further damage and infection. The 18-month-old boy who received the transplants has the most severe form of RDEB, which also causes skin to slough off on the inside of the body, affecting the mouth, oesophagus, and gastrointestinal tract. EB is genetic and severe forms are always fatal. Those who live to be young adults get an aggressive form of skin cancer called squamous cell carcinoma.

With the help of an EB mouse model and in collaboration with investigators at Columbia University, University of Minnesota researchers were able to correct the disease in mice using bone marrow. They tested various types of adult stem cells to determine which would give rise to the development of type VII collagen – the protein people with RDEB lack. One type of immature cells from bone marrow proved to be the best at producing anchoring fibrils that bind the skin to the body.

This is the first time physicians have approached EB from a systemic perspective, using transplant as a means to rid the body of the defective blood system and replace it with a healthy blood system that produces type VII collagen.

“Our goal is to determine the usefulness of stem cells, whether from the umbilical cord blood or adult tissues like bone marrow, in the treatment of human disease,” said John E. Wagner, M.D., professor of Paediatrics and director of the Division of Haematology, Oncology, and Blood and Marrow Transplantation and director of clinical research of the Stem Cell Institute at the University of Minnesota.

“There are hundreds of thousands of children and adults waiting for new breakthroughs in stem cell research, and time is never enough. In two years, the team was able to move this project forward remarkably fast – from testing in animal models to treating patients. Time will tell whether this risky treatment will work as effectively in humans. But, RDEB is a horribly debilitating, life-threatening disease with no existing curative therapy.”

The boy received both umbilical cord blood and bone marrow from a perfectly matched sibling. If the results mimic the animal model, doctors anticipate the healthy blood system will aid in the skin's ability to produce type VII collagen necessary to anchor the skin and lining cells of the gastrointestinal tract to the body. Doctors anticipate in early 2008 – approximately 100 days after transplant – they will be able to judge whether this the treatment helped.

“This represents a real change in thinking within the dermatological community. The possibility of this approach compels us to explore more broadly the way some skin diseases are typically treated,” said Maria Hordinsky, M.D., head of the Department of Dermatology at the University of Minnesota and member of the care team.

The paediatric BMT program at the University of Minnesota Children's Hospital, Fairview is internationally recognized for its pioneering work in umbilical cord blood and bone marrow transplantation, including the world's first successful BMT in 1968. In 2000, Wagner and team performed the first umbilical cord blood transplant from a sibling donor "created" after embryo selection.

The program leads the US in the use of umbilical cord blood in the treatment of adults and children and in the development of innovative treatments of various rare genetic diseases such as adrenoleukodystrophy (ALD) and Fanconi anaemia.

The transplant was done as part of a clinical trial funded by donations made to the University of Minnesota EB Fund and Children's Cancer Research Fund in Minneapolis.