Alopecia areata(AA) and Vitiligo
Alopecia areata is an acquired disease that produces similar circular alopecia patches, and in severe cases, the alopecia patches often enlarge repeated exacerbations and lightening. Although hair loss is generally considered to be the size of a 10-yen coin, the symptoms vary from those that spread over the entire head to severe cases that extend to the eyebrows, eyelashes, body hair, and other parts of the body (1). Patients themselves are deeply troubled by this condition because it greatly affects their impression of their appearance, and it greatly affects their quality of life.
The frequency of alopecia areata is estimated to be 1-2% of the population, with an estimated 150 million patients worldwide and 2.5 million in Japan. In the U.S., there are reports that 300,000 new cases of alopecia areata occur each year. Alopecia areata can occur at any age, but a quarter of patients begin at the age of 15 or younger, and there appears to be no difference between males and females.
Existing treatments include topical steroid injections, local immunotherapy, and topical agents, but there is still no fundamental cure. In addition, JAK inhibitors have recently been approved by the FDA, but there are concerns about serious side effects. Against this background, the development of therapeutic agents based on new mechanisms of action is desired.
Anti-IFNg aptamer TAGX-0003
TAGX-0003 is a oligonucleotide DNA aptamer that targets human IFNg containing our proprietary artificial base Ds and shows high affinity and specificity of 33 pM for human IFNg (2).
IFNg plays the most central role in the pathogenesis of autoimmune diseases, and in patients with alopecia areata, IFNg promotes the transition of hair epithelial cells to the catagen phase. IFNg also induces the production of IL-15, and CD8+ T cells activated by IL-15 attack hair follicles, causing hair loss (3, 4).
TAGCyx has already confirmed that the aptamer significantly suppresses hair regeneration, melanin formation, and the expression of MHC-I and II in ex-vivo studies using a mouse alopecia areata disease model in which humanized mice transplanted with human skin.
In addition, although oligonucleotide aptamers are medium molecular weight compounds, we have confirmed that they can penetrate the dermis by using ionic liquids, making it possible to develop them as an application agent, which would be beneficial in terms of side effects.
TAGCyx, in cooperation with its licensee CAGE Bio, is moving forward with pre-clinical testing of TAGX-0003, with the aim of entering clinical trials at an early date.
CAGE Bio Inc.（Worldwide, Except Japan）
- 日本皮膚科学会円形脱毛症診療ガイドライン2017年版： https://www.dermatol.or.jp/uploads/uploads/files/AA_GL2017.pdf
- Architecture of high-affinity unnatural-base DNA aptamers toward pharmaceutical applications. Matsunaga K. et al. Sci. Rep. 2015; 5: 18478.
- Understanding Autoimmunity of Vitiligo and Alopecia Areata. Jillian F. R. et al. Curr Opin Pediatr. 2016; 28: 463.
- Targeting the Janus Kinase Family in Autoimmune Skin Diseases. Michael D H. et al. Front Immunol. 2019; 10: 2342.