A research team of Soon Young Shin from Department of Biological Sciences at College of Sanghuh Life Science, Konkuk University (President Young Jae Jeon) announced on the 5th that they discovered the key gene that exacerbates atopic dermatitis and developed AB1711, a candidate substance for the development of innovative new drugs, confirming its possibility of restraining the formation of atopic cytokines.
The research was conducted by the support of Ministry of Science and ICT and National Research Foundation of Korea, and integrated Masters with PhD students, Hyun Jin Yeo and Sung Shin Ahn, shared co-first authorship. The research result was published online on February 3rd in Journal of Investigative Dermatology, the top 3.7% journal of dermatology. ▲ Professor Soon Young Shin, Yoong Ho Lim and Young Han LeeAtopic dermatitis is an inflammatory skin disease with painful itching which is difficult to treat as it lasts throughout the whole lifetime from adolescence to the elderly although it commonly occurs during infancy.
Atopic dermatitis causes extreme itching due to abnormal excessive response of the skin's immune system. This chronic disease requires consistent treatment and management as scratching damages skin barrier making it easier to be exposed to microorganisms as well as causing repetitive cycle of inflammatory response > itching > skin barrier damage > skin dryness > itching.
Although there are various virulence factors of atopic dermatitis including genetic, environmental and immunological factors, it is known that the symptoms get worse as a large number of inflammatory cytokines are mass produced. However, the inflammatory cytokine generation mechanism that leads to worsening atopic symptoms has not been identified yet, and it is difficult to develop atopic targeted treatments with greater efficacy and fewer side effects.
The research team (Professor Soon Young Shin, Yoong Ho Lim and Young Han Lee) has first discovered that EGR1 is a master regulator that produces atopic inflammatory cytokines of various types by using EGR1 gene-defective mouse (knockout mouse). Atopic inflammatory cytokines are known to aggravate itching and dermatitis. Thus, the research team hypothesized that atopic dermatitis can be cured if EGR1 activities are controlled, and developed AB1711 compounds that block the targeted gene DNA binding capability of EGR1 to prove the theory. ▲ The role of atopic dermatitis progression in EGR1 and EGR1 target effects in AB1711By demonstrating the fact that AB1711 compounds on animal models with atopic dermatitis can treat dermatitis and clinical symptoms such as itching, the research team confirmed the possibility of atopic targeted therapy for AB1711 compounds.
Professor Shin, the research director, said that, “AB1711 is currently patented for atopic treatment and we verified that it is not toxic even with high concentrations,” and “AB1711 could be developed as a new concept of targeted therapy that can selectively block the DNA binding function of EGR1, a transcription factor that exacerbates atopic dermatitis, to overcome the side effects and limitations of existing steroids or immunosuppressants.”
Professor Lim from Department of Integrative Bioscience and Biotechnology at Konkuk Institute of Science and Technology (KIT) who led the drug design stated that, “In order to make practical use of the research results, additional studies such as non-clinical experiments and human-applied clinical studies, including drug transfer biocompatibility and drug metabolism evaluation, are necessary.”