SINPAIN: A game changer for the treatment of osteoarthritis: a cost effective combined advanced therapy to treat knee osteoarthritis (SINPAIN)

SINPAIN：骨关节炎治疗的游戏规则改变者：一种治疗膝骨关节炎的经济高效的综合先进疗法 (SINPAIN)

• 批准号: 10038256
• 金额: $ 61.32万
• 依托单位: UNIVERSITY OF LIVERPOOL
• 依托单位国家: 英国
• 项目类别: EU-Funded
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10038256
• 关键词: SINPAIN; game; changer; treatment; osteoarthritis

According to the WHO Osteoarthritis (OA) is one major course of years lived with disability in the elderly and is considered a high-burden disease, which makes it a research priority in Europe. There is no cure for OA and SoA treatments need to be reconsidered. Current pharmacological interventions consist of analgesic, and anti-inflammatory drugs as well as intraarticular steroids and hyaluronic acid (IA-HA) with moderate efficacy and associated long-term side effects. New medications are thus needed both to alleviate pain and slow down disease progression. Taking advantage of the explosion of RNA technologies in the last years, SINPAIN aims to develop a pipeline of siRNA-based therapy built on the combination of current technologies (dynamic IA-HA and nanocarriers) that will be designed step-by-step in order to reach successful management of inflammation and innervation therapy for the treatment of early (grade 0-1) and later stages (grade 3-4) of knee osteoarthritis (OA). To do so, a nanoformulation composed of functional IA-HA that can be loaded with vectors, for the delivery of siRNA targeting IL1ß and NGF, and nanocarriers will be developed. In parallel, a large effort will focus on understanding the pathological mechanisms of OA. To validate efficacy in relevant potency assays, 3D coculture models will be developed with human cells and tested in unique bioreactors mimicking joint environments and biomechanics. With the identified cell targets, IA-HA will be modified with an immunomodulator peptide which will activate the adaptive immune response, responsible for OA regeneration. The 4 pipeline products of SINPAIN will be validated in vivo in a relevant OA model with SoA techniques that will demonstrate the reduced inflammation and pain, as well as the cartilage regeneration for the last product. Taking advantage of all the data obtained during the project, a decision-making tool based on machine learning will be validated to offer patients a personalized therapy.

据世界卫生组织称，骨关节炎（OA）是老年人残疾的一个主要病程，被认为是一种高负担疾病，这使其成为欧洲的研究重点。 OA 无法治愈，需要进行 SoA 治疗。目前的药物干预措施包括镇痛药、抗炎药以及关节内类固醇和透明质酸（IA-HA），其疗效中等，但存在相关的长期副作用，因此需要新的药物。为了减轻疼痛并减缓疾病进展，SINPAIN 旨在结合现有技术（动态 IA-HA 和纳米载体）开发一系列基于 siRNA 的疗法。逐步设计，以便成功管理炎症和神经支配治疗，以治疗膝骨关节炎 (OA) 的早期（0-1 级）和晚期（3-4 级）。纳米制剂由可装载载体的功能性 IA-HA 组成，用于递送靶向 IL1ß 和 NGF 的 siRNA，同时，将开发大量努力来了解 OA 的病理机制，以验证相关功效。效力测定、3D 共培养模型将与人体细胞一起开发，并在模拟关节环境和生物力学的独特生物反应器中进行测试，根据确定的细胞靶标，IA-HA 将用免疫调节肽进行修饰。这将激活适应性免疫反应，负责 OA 再生。 SINPAIN 的 4 个管道产品将在相关 OA 模型中使用 SoA 技术进行体内验证，该技术将证明炎症和疼痛的减轻以及最后的软骨再生。利用项目期间获得的所有数据，将验证基于机器学习的决策工具，为患者提供个性化治疗。