- Gene therapy
helps restore 80 percent of epidermis of a 7 year old boy suffering from a
genetic skin disease.
bullosa is caused due to a defect in protein-forming genes that are
required for skin regeneration.
- Epidermal skin
cells were corrected with the correct copy of the gene to create the
transgenic skin that was transplanted on to the patient.
For the first time in skin transplantation, a large surface area of
damaged skin was transplanted with transgenic skin derived from genetically
modified epidermal stem cells from the patient.
The gene therapy was used
to treat a seven year old boy suffering from extensive skin damage due to a
genetic condition called epidermolysis bullosa
The procedure was performed by teams at the Ruhr-Universität Bochum's burn unit
and the Center for Regenerative Medicine at the University of Modena (Italy)
and published in Nature.
It is a congenital skin disease that causes
extensive damage to the epidermal layer of the skin
. It is caused due to
genetic defects in protein forming genes that are crucial in skin regeneration.
Even the slightest of stress to the skin can result in blisters, wounds and
skin loss with scar formation. There is presently no cure for the disease. The
disease reduces quality of life and can be life threatening depending on
disease severity. In advanced cases, it can even affect internal organs leading
to organ dysfunction.
Hassan, a seven year old boy suffering from
epidermolysis bullosa was brought into the intensive care unit at Katholisches
Klinikum Bochum in June 2015 when 60 percent of his epidermis was already lost.
This is what Dr Tobias Rothoeft, Consultant at the
University Children's Hospital at Katholisches Klinikum Bochum had to say about
Hassan's condition; "He suffered from severe sepsis with high fever, and
his body weight had dropped to a mere 17 kilogrammes - a life-threatening
When all medical and surgical approaches failed in treating the child,
the team decided to perform an experimental approach--using the child's own stem
cells to produce transgenic skin
which was transplanted on to the child.
Previously, a phase I/II clinical trial provided promising evidence that local
transplantation of transgenic skin can generate a functional epidermis
This showed permanent (the longest follow-up being of 12 years) correction of
skin lesions in patients with epidermolysis bullosa. However, the tested area
of transplanted skin was very small to substantially improve the patient's
quality of life.
‘Eighty percent of a child’s epidermal skin area was transplanted with the transgenic skin derived from the keratinocytes.’
In the current study, almost the entire epidermis, approximately 0.85
square meters, of the seven year old boy was transplanted with transgenic skin
derived from keratinocyte cultures.
The keratinocytes were taken from the
non-blistering part of the child's body and cultured in the laboratory. Then,
the defective copy of the gene was replaced with the correct copy using
The developed transgenic skin was then transplanted
on to the wound sites of the patient, including the arms and legs, entire back,
flanks, and partially to the stomach, neck and face.
Results of the gene therapy
There was tremendous improvement in Hassan's condition after the
transplant. Today, almost two years since the therapy began, the transplanted
epidermis remains resistant to stress with no scars and hair formation is at
its beginning stages.
Hassan now attends school and has a social life.
"This approach has enormous potential for
research and development of new therapies for the treatment of epidermolysis
bullosa as well as other diseases and trauma causing large skin defects"
says Tobias Hirsch.
- Tobias Hirsch, Tobias Rothoeft, Norbert Teig, Johann W. Bauer, Graziella Pellegrini, Laura De Rosa, Davide Scaglione, Julia Reichelt, Alfred Klausegger, Daniela Kneisz, Oriana Romano, Alessia Secone Seconetti, Roberta Contin, Elena Enzo, Irena Jurman, Sonia Carulli, Frank Jacobsen, Thomas Luecke, Marcus Lehnhardt, Meike Fischer, Maximilian Kueckelhaus, Daniela Quaglino, Michele Morgante, Silvio Bicciato, Sergio Bondanza, Michele De Luca. Regeneration of the entire human epidermis using transgenic stem cells. Nature, (2017); DOI: 10.1038/nature24487