Relief Therapeutics Holding AG (RLFTF)

[changes_iv]

It is important to bear in mind that RA is a dynamic disease in its development, so a complete understanding of how RA develops over time is important to set up therapies that prevent disease progression rather than treating its symptoms [35]. The importance of the neuroimmune network in joint homeostasis has been shown. Indeed, several neuropeptides identified in joint tissues, including vasoactive intestinal peptide (VIP), have been suggested to have a role as neuroosteological regulators in bone metabolism. VIP is a homeostatic and immunoregulatory peptide involved in the control of both innate and adaptive immune response. It has only one chain of 28 amino acids, with some residues crucial to its functions, which sequence is highly conserved during evolution. It belongs to the secretin/glucagon family of peptides which share an a-helix structure [36]. This neuropeptide can act locally or systematically as it is produced by sympathetic nerve endings, lymphocytes, or even FLS in the joint [37, 38]. VIP is involved in a broad range of functions through its binding to its specific G-protein-coupled receptors, VPAC1 and VPAC2 [39]. Healing effects of exogenous administration of VIP in animal models of inflammatory/autoimmune diseases have been described; specifically, VIP prevents arthritis in a CIA model through its anti-inflammatory and immunomodulatory actions [40, 41]. In humans, “ex vivo” effects of VIP have been demonstrated in lymphocytes, macrophages, and FLS [21, 38, 42]. In summary, VIP is a microenvironment mediator capable of modulating all the stages mentioned above in RA from the arrival of pathogens to the differentiation of Th cells. It exerts a direct antimicrobial activity against a variety of pathogens [43, 44] and modulates TLR expression in several cells, even in FLS from RA patients [45–47]. In addition, VIP decreases proinflammatory mediators in lymphocytes and FLS from RA patients [21, 38, 48–50] and modulates the differentiation of several Th cells from RA patients, including a decrease in the pathogenic profile and plasticity of some of them [21, 50, 51]. In addition to the role of VIP in “ex vivo” samples from RA patients, endogenous VIP also plays a major role in patients with RA, allowing to stratify patients with early RA for therapeutic decision making in the “window of opportunity” [52]. VIP gene polymorphisms, associated with its serum levels, predict treatment requirements in early rheumatoid arthritis [43, 53]. Indeed, lower levels of its receptor, VPAC1, in PBMCs are associated with more severe inflammation and higher disease activity in RA patients [54].

Taking all this into consideration, this review provides a deep description of the role of this anti-inflammatory mediator, VIP, in the differentiation and function of Th subsets in rheumatoid arthritis, capable to modulate all the stages between the arrival of pathogens and the differentiation of Th cells in RA.

https://www.hindawi.com/journals/jir/2018/6043710/

The global rheumatoid arthritis therapeutics market size is expected to reach USD 30.4 billion by 2025, according to a new report by Grand View Research, Inc., expanding at a CAGR of 4.6% during the forecast period.

https://www.grandviewresearch.com/press-release/global-rheumatoid-arthritis-therapeutics-market