Autoimmune Disorders
Autoimmune disorders arise when the immune system mistakenly attacks healthy cells and tissues. Psoriasis, a chronic skin condition, results from immune dysfunction targeting skin cells. Other autoimmune diseases like rheumatoid arthritis and lupus affect various organs. Treatment often involves immunosuppressants to manage symptoms and reduce inflammation. Immunosuppressive therapies can lead to long-term side effects such as increased susceptibility to infections and potential organ damage. We are working on the development of antisense oligonucleotide therapy for such conditions.
PSORIASIS
Psoriasis is a chronic autoimmune skin disorder affecting about 2-3% of the global population. It's characterized by red, scaly patches on the skin, often accompanied by itching and discomfort. The disease's molecular mechanism involves an overactive immune system, where T cells mistakenly attack healthy skin cells, triggering rapid skin cell turnover. This leads to the formation of thick, inflamed patches. Psoriasis severity varies, ranging from mild cases with limited skin involvement to severe forms affecting large areas of the body. Additionally, psoriasis is associated with systemic inflammation, potentially leading to complications like psoriatic arthritis and increased risk of cardiovascular disease.
Genes Under Investigation
IL-16 (Interleukin-16)
Interleukin-16 (IL-16) is a pro-inflammatory cytokine crucial in immune responses, attracting various immune cells to sites of inflammation by binding to the CD4 receptor. In psoriasis, IL-16 contributes to disease pathogenesis by recruiting CD4+ T cells, sustaining inflammation, and promoting keratinocyte proliferation. IL-16's involvement suggests its potential as a biomarker for disease activity and a target for therapeutic intervention. Inhibiting IL-16 activity or its interaction with CD4 could be explored as a treatment strategy. Developing IL-16 inhibitors may offer new therapeutic avenues for psoriasis, especially for non-responsive patients. Clinical trials are needed to assess safety and efficacy, while further research into IL-16's role in psoriasis may uncover additional therapeutic targets.
IL-17RD (Interleukin-17 receptor D)
Interleukin-17 receptor D (IL-17RD), a member of the IL-17 receptor family, participates in IL-17 cytokine signaling pathways crucial in inflammatory diseases like psoriasis. It modulates NF-κB activation and pro-inflammatory gene expression. In psoriasis, IL-17RD amplifies IL-17 signals, influencing keratinocyte responses and exacerbating inflammation. IL-17RD's expression levels could serve as a biomarker for disease severity or therapeutic response, and targeting IL-17RD may offer a new avenue for psoriasis treatment. Developing inhibitors and conducting clinical trials are crucial steps in exploring IL-17RD as a therapeutic target. Further research is needed to understand IL-17RD's precise role in psoriasis and its interactions within the IL-17 signaling pathway.
IL-5RA (Interleukin-5 receptor alpha)
Interleukin-5 receptor alpha (IL-5RA) is integral in eosinophil activation, crucial in allergic responses and asthma. Associated with Th2 immune responses, it plays a role in defense against helminth infections. While its involvement in psoriasis is less clear, potential mechanisms include eosinophil recruitment and interaction with other cytokines. IL-5RA's role in psoriasis may be secondary, with implications for biomarker use and therapeutic targeting, particularly in variants with eosinophilic inflammation. Currently, IL-5RA targeting focuses on conditions like asthma. Clinical trials are needed to explore its efficacy and safety in psoriasis treatment. Further research is vital to understand IL-5RA's role in psoriasis and its interactions within the cytokine network.
IL-6R (Interleukin-6 receptor)
Interleukin-6 receptor (IL-6R) binds IL-6, regulating immune responses and inflammation. IL-6R exists in membrane-bound and soluble forms, initiating signaling pathways with both pro- and anti-inflammatory effects. In psoriasis, an autoimmune skin condition, IL-6 contributes to inflammation, T cell activation, keratinocyte proliferation, and angiogenesis. IL-6 and soluble IL-6R levels could serve as biomarkers for disease activity or treatment response in psoriasis. Targeting IL-6R with inhibitors like Tocilizumab may offer new treatment options, pending clinical trials to assess efficacy and safety. Further research into IL-6R's role in psoriasis is crucial for understanding disease mechanisms and developing targeted therapies.
IL-18RA (Interleukin-18 receptor alpha)
Interleukin-18 receptor alpha (IL-18RA) forms a receptor complex with IL-18, playing a crucial role in immune responses. In psoriasis, an autoimmune skin condition, IL-18RA contributes to inflammation and abnormal skin cell growth. By promoting Th1 and Th17 responses and inducing inflammatory cytokine production, IL-18RA exacerbates psoriatic pathology. IL-18 and IL-18RA levels could serve as biomarkers for disease severity or treatment response. Targeting IL-18RA presents a potential therapeutic strategy for psoriasis treatment. Developing IL-18RA inhibitors warrants further research and clinical trials to assess safety and efficacy, providing new options for patients resistant to current therapies. Understanding IL-18RA's role in psoriasis and its interactions with other cytokines is crucial for advancing treatment approaches.