Patients with a rare genetic skin condition have been successfully treated, for the first time, using a novel gene therapy.
Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic condition characterised by the absence of collagen in the skin due to the inheritance of a faulty copy of the COL7A1 gene from both parents. Researchers at Stanford University used a genetically engineered form of the herpes simplex virus (HSV) to deliver a functional copy of the COL7A1 gene into skin cells, thereby correcting their ability to properly synthesise collagen. The genetically altered virus was loaded into a gel which could be easily applied to the participants' wounds, much like any topical treatment.
'The wounds heal quickly but, even more importantly, they stay closed,' said Dr Peter Marinkovich, lead author of the study. 'The therapy strengthens the skin and breaks the painful and destructive cycle of wound opening and closing that patients with epidermolysis bullosa experience.'
Typically, collagen functions to bind the separate layers of the skin together. However, in patients with RDEB the unbound layers of skin rub against each other leading to blistering and tearing. People with the disease are called 'butterfly children' as their skin is so fragile that the slightest touch can lead to blistering.
In the research, published in Nature Medicine, nine participants had the gene therapy gel applied to one of their skin wounds, while an inactive gel was applied to a different wound to allow for direct comparison. Following a three-month trial period, 71 percent of wounds treated with the gene therapy gel had completely healed, with no adverse side-effects reported. Contrastingly, only 20 percent of wounds treated with the inactive gel had completely healed.
Vincenzo Mascoli described living with RDEB as 'very painful.' He had open wounds all over his body, with one covering his whole back, which was treated during the trial. 'The gene therapy was very good for my back. Now, I can have a bath without it burning my skin... I hope I will be able to use it on the rest of my body.'
Until now, previous trials to treat skin diseases through direct gene transfer were unable to achieve sufficient clinical alteration of disease presentation. Furthermore, alternative viral gene therapy vectors have provoked an immune response in patients, especially following repeat treatment. Using HSV can minimise both issues, as not only does it efficiently infect skin cells but it also has innate immune evasive properties, which allow it to infect cells while remaining largely undetected by the immune system.
As skin cells naturally die, they are replaced by new cells which will no longer possess the functional COL7A1 gene. However, this gel only requires reapplication every six months, and can be performed during routine bandage changes.
The gel has now completed a phase 3 trial and the researchers intend to apply for approval from the US Food and Drug Administration. If approved, the gene therapy gel would be widely available and is proposed to significantly improve the quality of life for patients with RDEB.
Sources and References
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First ever gene therapy gel corrects rare genetic skin condition
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In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial
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Gene-therapy gel shows promise for blistering skin disease in clinical trial
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New gene-therapy gel shows promise for treating rare 'butterfly disease'
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DNA-spiked gel heals the skin wounds of 'butterfly children'
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