Dry eye related to Sjögren's syndrome
Disease
Sjogren's syndrome is an organ-specific autoimmune disease targeting the lacrimal and salivary glands, but it is also a systemic autoimmune disease with systemic organ involvement. Dry eye related to Sjögren's syndrome, together with xerostomia, causes severe dryness, which, when severe, significantly impairs quality of life, such as lack of tears, eye burning, and eye irritation, and has been designated an intractable disease in Japan (1).
Patient
The number of patients with Sjögren's syndrome in Japan is estimated to be approximately 68,000, but the potential number is estimated to be 100,000~300,000. Of these, about 60% are patients with primary Sjögren's syndrome, which is not complicated by collagen disease, and about 45% of patients with primary Sjögren's syndrome have only symptoms of dry eyes and dry mouth.
Current Treatment
Current treatments include methods to (1) promote tear secretion, (2) replenish tears, (3) prevent tear evaporation, and (4) decrease tear discharge. Although some treatments are highly effective, existing eye drop treatments are not fundamental treatments and have problems such as side effects including itchy eyes and eye irritation, and the need for a long period of time before the medicinal effects are manifested.
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 a most central role in the pathogenesis of autoimmune diseases, and overexpression of IFNg has been observed in patients with dry eye. IFNg is known to induce goblet cell apoptosis and predominantly decrease mucin expression in dry eye (3). It has also been reported that IFNg-mediated signaling is involved in dry eye in Sjögren's syndrome (4), and targeting IFNg may be one of the fundamental treatments for the disease.
TAGCyx has already confirmed that mouse surrogate aptamer improved the clinical scores at an early stage of treatment and pathological findings and the model-induced decrease in goblet cell count and CD4+ T cell increase to normal levels in an animal study of a mouse model of dry eye disease.
In addition, oligonucleotide acid aptamers are highly water soluble and stable at room temperature, making their development as eye drops an advantage.
TAGCyx is moving forward with non-clinical studies of TAGX-0003 and aims to enter clinical trials as soon as possible.
[Reference]
- 公益財団法人 難病医学研究財団/難病センターWeb site： https://www.nanbyou.or.jp/entry/111
- Architecture of high-affinity unnatural-base DNA aptamers toward pharmaceutical applications. Matsunaga K. et al. Sci. Rep. 2015; 5: 18478.
- Aqueous Tear Deficiency Increases Conjunctival Interferon-γ (IFN-γ) Expression and Goblet Cell Loss. Stephen C. et al. Invest Ophthalmol Vis Sci 2015; 56: 7545.
- Interferons and Dry Eye in Sjögren’s Syndrome. Ogawa Y. et al. Int J Mol Sci. 2018; 19: 3548.