METHYLOMIC_DNA methylation markers to predict treatment success of biologicals in Crohn’s disease

METHYLOMIC_DNA 甲基化标记可预测克罗恩病生物制剂的治疗成功率

• 批准号: 10063907
• 金额: $ 67.03万
• 依托单位: KING'S COLLEGE LONDON
• 依托单位国家: 英国
• 项目类别: EU-Funded
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10063907
• 关键词: METHYLOMIC_DNA; methylation; markers; predict; treatment

Monoclonal antibodies have become a mainstay of therapy in common immune-mediated diseases (IMID) including Crohn’s disease(CD), rheumatoid arthritis (RA), and psoriasis (PsO). Current therapeutics include antibodies (“biologicals”) targeting inflammatoryproteins such as Tumor Necrosis Factor (adalimumab), leukocyte trafficking (vedolizumab), or IL-12/IL-23 (ustekinumab). At presenthowever, it cannot be predicted which biological will be effective in an individual patient, with only <40% of patients showing primaryresponse to any given therapeutic. Treatment failure is associated with disease complications, and increased health care costs.. Hencethe overwhelming need for predictive biomarkers to guide personalised medicine in IMID is evident. No biomarker to target therapyis validated in clinical practice. In METHYLOMIC, we build on multiple previous cohort studies in which we confirmed epigeneticbiomarkers (specifically DNA methylation) as the most stringent predictor of response to biological therapy, zooming in on CD.Specifically, we discovered and validated differential DNA methylation profiles in peripheral blood as biomarkers of response/deepremission for 3 approved biologicals in CD. Through the use of machine learning algorithms, treatment response could be predicted withup to 93% accuracy for each biological for CD, and RA. METHYLOMICS is committed to bringing personalised treatment-selection inCD and other IMID to clinical practice. We have teamed up clinical, epigenetic, and DNA diagnostics experts, patient organisations, andcompanies across Europe, for further validation studies, develop a marketable rapid targeted methylation assay that we than validate in aunique prospective randomised clinical trial for CD. Efficiency and cost-effectiveness is assessed in great detail and regulatory approvalis guided by experts to assure delivery of the first epigenetic kit personalised treatment of CD.

单克隆抗体已成为常见免疫介导疾病（IMID）（包括克罗恩病（CD）、类风湿性关节炎（RA）和银屑病（PsO））的主要治疗手段。目前的治疗药物包括靶向炎症蛋白的抗体（“生物制剂”），如肿瘤坏死因子（阿达木单抗）、白细胞运输（Vedolizumab）或IL-12/IL-23（优特克单抗）。目前，还不能预测哪种生物制剂对个体患者有效，只有<40%的患者对任何给定的治疗药物显示出初步反应。治疗失败与疾病并发症有关，并增加了医疗保健费用。因此，对预测性生物标志物的压倒性需求，以指导IMID的个性化药物是显而易见的。在临床实践中没有生物标志物对靶向治疗进行验证。在METHYLOMIC中，我们建立在多个先前的队列研究的基础上，在这些研究中，我们证实了表观遗传学生物标志物（特别是DNA甲基化）是对生物治疗反应的最严格预测因子，放大了CD。具体来说，我们发现并验证了外周血中的差异DNA甲基化谱作为3种批准的CD生物制剂的反应/进展的生物标志物。通过使用机器学习算法，可以预测CD和RA的每种生物制剂的治疗反应，准确率高达93%。METHYLOMICS致力于将CD和其他IMID的个性化治疗选择带入临床实践。我们已经与欧洲的临床、表观遗传学和DNA诊断专家、患者组织和公司合作，进行进一步的验证研究，开发出一种可上市的快速靶向甲基化检测方法，然后在一项独特的CD前瞻性随机临床试验中进行验证。效率和成本效益进行了非常详细的评估，并在专家的指导下获得监管批准，以确保提供第一个CD的表观遗传试剂盒个性化治疗。