Gene therapy for butterfly children: 5-year follow-up published in the New England Journal of Medicine

Epidermolysis bullosa (EB), better known as butterfly baby disease, is a genetic disorder that involves the continuous formation of bullous lesions on the skin, due to very small mechanical trauma and minimal rubbing, which strongly impact the quality of life of these patients. Depending on the type of mutated gene, it is distinguished in different forms, of which the most severe are Junctional and Dystrophic.

In 2017, the story of Hassan, a Syrian “butterfly child” treated in Bochum (Germany), with the gene therapy developed by Prof. Michele De Luca, director of the Center for Regenerative Medicine “Stefano Ferrari” of Unimore and co-founder of the university spin-off Holostem, went around the world.

After the failure of all attempts to cure the little patient, who had lost most of his skin due to repeated infections and was kept under pharmacological sedation for unbearable pain, the doctors in Bochum had turned to the team from Modena in search of help. Having obtained approval for compassionate use from the German regulatory authorities, nearly one meter of genetically corrected epidermis flaps were transplanted between September and November 2015, saving the little patient and allowing him a quality of life he never had before.

From 2015 to date, Hassan has been followed clinically by physicians in Bochum and Muenster, Germany, while molecular biological follow-up has been performed in Modena, Italy. The results of this long follow-up (5 years) were published today in The New England Journal of Medicine, one of the most prestigious medical journals in the world.

The study confirms that genetically corrected epidermis cultures can reconstruct large areas of the body in patients with Junctional Epidermolysis Bollosa (the form from which Hassan was affected) over many years.

Since the epidermis, which is a tissue subject to frequent renewal even in healthy individuals, renews itself approximately every 1-2 months, we must assume that Hassan’s skin went through about 30-60 cycles of renewal while maintaining its integrity and functionality, in accordance with what we saw in a first patient treated in 2006, without ever manifesting any blistering lesions in the treated areas.

Several clinical, cellular and molecular tests have demonstrated the adequacy of numerous parameters, including the reconstruction of the skin’s immune system, the presence of an intact skin barrier, an adequate level of skin hydration with the presence of sebaceous and sweat glands. And tests performed on the patient’s own cells demonstrated the safety of the treatment, confirming results obtained in vitro in more than 30 years of basic research.

The long-term clinical results, which show a stable and robust transgenic epidermis after more than 5 years of follow-up – explains Prof. Michele De Luca of Unimore – show us that we are on the right track and encourage us to continue with even greater determination our efforts to develop a gene therapy platform to also attack other severe forms of EB, such as Dystrophic EB, and other monogenic diseases such as ichthyosis”.

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