Sunburns are terrible. The skin blisters and peels. Even a light brush from putting on clothes or tucking into bed sheets is agony.

Now imagine having those blisters at just six months old. But the sun isn’t the culprit; your genes are.

Thousands of people in the US suffer from dystrophic epidermolysis bullosa (DEB), a rare genetic disorder that severely affects the structure and integrity of the skin and eyes. Children with this illness have skin as delicate as wet tissue paper. Chronic painful blisters and wounds, sometimes even in their throats, are an everyday part of their lives from birth.

The underlying cause of DEB is a single gene mutation that impacts a critical protein responsible for maintaining skin integrity. This genetic error makes the illness an ideal candidate for gene therapy. However, due to the fragility of the skin, traditional gene therapy methods involving injections are difficult to tolerate.

But what if a genetic moisturizer could be the solution?

In a significant development, the FDA has recently approved the first rub-on gene therapy for DEB. Similar to applying aloe vera to treat sunburns, this therapy comes in the form of a gel that is gently massaged onto blisters and wounds to aid in healing. Named Vyjuvek, it directly delivers healthy copies of the mutated gene to damaged skin. An alternative version of the therapy is formulated as eye drops to reconstruct the delicate architecture of the eyes and improve vision.

Multiple clinical trials involving patients ranging from infants to middle-aged individuals have demonstrated promising results. After six months of treatment, the therapy reduced painful blisters, and over two-thirds of the patients’ wounds completely healed with weekly massages, compared to just one out of five wounds treated with a placebo. Patients also experienced improved eyesight, enabling them to engage in activities they were previously unable to enjoy, such as playing online games.

This groundbreaking therapy not only offers hope to those with rare skin conditions but also paves the way for future advancements in gene therapy. By targeting collagen, a critical protein for maintaining skin structure and elasticity, the rub-on treatment holds potential for the development of next-generation moisturizers to combat signs of aging like fine lines and crow’s feet. Krystal Biotech, a Pittsburgh-based subsidiary that developed Vyjuvek, is already expanding its reach into the cosmetics industry.

However, the significance of this achievement goes beyond superficial beauty enhancements. According to Krish S. Krishnan, CEO of Krystal Biotech, the FDA’s approval of Vyjuvek “ushers in a whole new paradigm to treat genetic diseases.”

Vyjuvek joins the ranks of other approved gene therapies that have primarily focused on battling blood cancers and disorders. These treatments typically involve extracting immune or red blood cells from a patient, genetically enhancing them, and reintroducing them into the body. Some are engineered to target cancer cells, while others aim to boost the oxygen-carrying capacity of red blood cells.

Compared to deeper organs, the skin presents unique challenges as a target for gene therapy due to its multiple protective layers. Previous treatments for DEB involved grafting genetically engineered skin onto patients, an intensive procedure that often required extended hospital stays or medically-induced comas.

To overcome these challenges, the research team behind Vyjuvek took a clever approach. They first identified the specific genetic error responsible for DEB, which led them to the COL7A1 gene, encoding a type of collagen critical for skin stability. By genetically packaging a healthy version of the COL7 gene into a modified harmless herpes simplex virus (HSV-1), they created a delivery system capable of penetrating the skin without causing harm or replication.

In clinical studies, the gel-based gene therapy, known as B-VEC, successfully healed nearly 70 percent of painful wounds and significantly reduced pain in patients. However, it is important to note that the treatment is not a cure. Since the skin constantly renews itself with new cells carrying the same genetic defects, regular application of the gel by healthcare professionals is required to maintain its effectiveness.

While the cost of gene therapy can be substantial, with treatments reaching millions of dollars, the approval of Vyjuvek brings hope and relief to the DEB community. Brett Kopelan, Executive Director of debra, an organization that supports individuals with the illness, expressed gratitude for the safe and effective treatment, stating that it marks a monumental milestone in the treatment of DEB.

Moreover, this study expands the landscape of gene therapy by introducing rub-on therapies, with eye drops for treating genetic eye disorders expected to follow soon.

Looking ahead, Krystal Biotech aims to leverage its breakthrough gene therapy technology to enter the lucrative skincare industry, targeting aging and damaged skin. Although the skin’s natural barrier poses challenges, if successful, this treatment may revolutionize skincare by providing highly efficient solutions in a bottle, eliminating the need for invasive procedures.

Vyjuvek represents a remarkable advancement in the field of gene therapy and offers hope not only for individuals with genetic skin disorders but also for the future of medical treatments.

By Impact Lab