A nine-year-old in Germany’s Ruhr Valley is doing what kids do: playing football, having fun with friends, and going to school. Two years earlier, he was dying of a rare and brutal genetic skin disease, confined to a hospital bed. In a landmark paper online this week in Nature, scientists and clinicians detail her astonishing recovery (T.Hirschetal.Naturehttp://dx.doi.org/10.1038/nature24487;2017).
The boy had junctional epidermolysis bullosa or JEB. They, like others with the disease, carried a mutation in a gene that controls the integrity of the skin. The doctors could only try to ease her suffering because about 80% of her skin had simply fallen off.
A team of Italian researchers came to his aid by combining stem-cell techniques with gene therapy. As a young scientist at Harvard Medical School in Boston, Massachusetts, in the 1980s, Michele De Luca – lead author of the new study – observed that pioneers in skin regeneration developed tiny sheets of skin from cells taken from burn patients. learn to do, and use them in grafts.
He extended the work in Italy, applying new genetic and stem-cell technologies. They developed methods to generate stem cells from human skin, replace disease-causing genes in them, and grow sheets of healthy skin on scaffolds in the laboratory.
He chose JEB for his first clinical trial, which he registered with the Italian Medicines Agency in 2002. Four years later, he reported his first breakthrough, in which he created patches of healthy skin from biopsies to replace small areas of skin.
Foot of a patient as in JEB (F. Mavilio et al. Nature Med. 12, 1397–1402; 2006). New European Commission regulations introduced in 2007 required them to halt the project, while they introduced ‘good manufacturing practices’ (GMP) and a spin-off company to meet demands for stronger oversight of cell-based treatments. Build facilities to follow.
One company focused its team on a different type of stem-cell therapy, with the potential to get the product to market faster. Holoclear, a treatment that replaces the cornea of the eye as a form of blindness, became the world’s first commercial stem-cell therapy in 2015.
A few months later, at the University of Modena, De Luca received a sudden call from doctors in Germany who were trying to treat the little boy. Because the therapy was in a clinical trial, although on a hold at the time, and because De Luca could provide GMP services, German regulatory authorities immediately approved the unilateral compassionate use of JEB therapy.
Surgeons in Germany sent a skin biopsy to Modena, and it was followed by two major skin transplants. Six months after the initial biopsy, the boy returned to school. During the several months that followed, he didn’t have that much blistering, and he likes to show off his ‘new skin’.
This major clinical development was based on decades of basic research. Clinical data collected during the 21 months of follow-up following the boy’s treatment have led to major insights into human skin biology, as discussed in an accompanying News and Views. /nature 24753; 2017). For example, normal regeneration of the epidermis is guided by only a few stem-cell clones that can self-renew.
By their nature, gene therapy and highly personalized treatments using products derived from an individual’s stem cells are likely to be applicable only to a subset of patients. Although the report presents a treatment for one patient, it is a classic case of researchers standing on the shoulders of others.
This project, for example, relies on long-term follow-up of a patient treated in 2006, as well as parallel studies that support the development of devices for ex vivo gene therapy and implantable sheets of the epidermis in vitro. Underlines.
This work is a technological achievement and an example of how translational medicine should be conducted. This involves informing clinic and clinician research with seamless collaboration between doctors, scientists, regulators and technicians at multiple levels – a particularly important aspect in areas such as stem-cell biology.
This requires the highest standards of scientific and ethical diligence. Similar treatments for other diseases are being introduced in other laboratories as well. Nature is happy to celebrate and support such an enterprise.