Network Pharmacology Approaches in the Treatment of Ankylosing Spondylitis: Mechanistic Insights and Therapeutic Targets

Ankylosing spondylitis (AS) is a late progressive inflammatory disease with the hallmark of predominantly axial spine involvement, causing pain, stiffness, and ultimate bony fusion of vertebral bodies. In late stages, most patients need surgical intervention by arthroplasty. The clinical presentation of the disease is characterised by signs like inflammatory back pain, sacroiliitis, enthesitis, and extraspinal systemic disease, with the vast majority having a very high association with HLA-B27 positivity. The pathogenesis of AS is a complex interaction between inflammatory and autoimmune processes. Pharmacologic management of AS at present comprises NSAIDs, DMARDs, glucocorticoids, analgesics, and biologics targeting cytokines such as TNF-alpha and IL-17. Despite their ability to influence disease and clinical features, their ability to arrest structural progression remains limited. An extended application is also regularly associated with unwanted side effects such as risk of infection, gastric distress, osteoporosis, and an unjustifiable cost burden. Methazolamide, a carbonic anhydrase (CA) inhibitor, has recently been shown in new research to have new therapeutic potential. Also, Gene Set Enrichment Analysis (GSEA) and network pharmacology strategies. Target genes for the perpetrator, like CA1, PTGS2, JAK2, ESR1, GSK3Beta, and NOS2, form the core of its mechanism as they are implicated in inflammation, angiogenesis, and bone remodelling.