Researchers discover natural gene therapy in the treatment of an intractable skin disease

According to researchers from Hokkaido University and their collaborators in Japan, mutations of pathogenic genes at the origin of a type of persistent skin disorder can be eliminated from certain parts of patients' skin as they age. This represents a form of natural gene therapy.

In general, there is no basic treatment method that can cure diseases caused by a genetic defect, as it is difficult to eliminate certain genetic mutations from all affected cells. Loricrin keratoderma (LK) is one of these diseases; caused by mutations of loricrin, it is characterized by dry skin, thickened and scaly from birth. Only symptomatic treatments are available to relieve conditions that cause difficulties in the daily life of patients. Until now, doctors have not been able to treat the bad.

In a study published in Alliance of Life Sciences, the research team, including Toshifumi Nomura and Shotaro Suzuki of the University of Hokkaido, observed patients' skin for an extended period. They discovered that LK patients had a normal-looking skin area dotted around their body. The tissue histology of these regions is examined and the presence of loricrin mutations in DNA extracted from the epidermis and dermis is verified.

The study revealed that the areas of skin that appeared normal were in fact skin that had returned to normal and that, surprisingly, the mutant loricrin that patients were supposed to have had since birth had disappeared. Detailed DNA sequence badyzes revealed that the mutation had disappeared because of somatic recombination – a type of recombination DNA that causes the exchange of strands of DNA-containing sequences Similar. Normal skin has remained in the same place for several years at least. The results therefore suggest that gene mutations are eliminated from stem cells that provide new cells in the epidermis.

The study also revealed that cells containing normal loricrin have a higher reproductive capacity and are more likely to form colonies than cells containing loricrin mutant. This survival advantage could be the reason why normal cells have become visible on the skin of patients.

"If we could elucidate the mechanism of somatic recombination common in epidermal cells and find a way to artificially induce it, this could lead to the development of a new method of treating the keratoderma of loricrin, and potentially 39, other genetic diseases, "said Toshifumi. Nomura.