引领科学超越COPD的症状控制

最后更新:
2022年10月12日

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下一代疗法

 


写的:

玛丽亚Belvisi

高级副总裁兼研究和早期发展主管 & 免疫学、澳门葡京网赌游戏


慢性阻塞性肺疾病(COPD)是全球第三大死亡原因,1 40岁以上的人中有十分之一患有此病.2 虽然澳门葡京赌博游戏对慢性阻塞性肺病生物学的理解已经取得了相当大的进展, 近几十年来,慢性阻塞性肺病的治疗进展缓慢.

 

作为呼吸医学领域的长期领导者, we are bringing inhaled therapy to COPD and leading the science to deliver next generation treatments 与 the potential to reduce exacerbations, 住院和死亡率. We are committed to developing new therapies that target the underlying drivers of COPD to move beyond exacerbation prevention and symptom control to slow and reverse disease progression by enhancing lung regeneration.


除了治疗, we are working 与 governments and policy makers around the world to address systemic challenges and make COPD a public health priority – including Act on COPD, a programme designed to educate and provide resources to change the mindset of COPD care and to reduce 住院和死亡率. 在一个单独的倡议中, 澳门葡京赌博游戏正在合作开展首个COPD质量改善项目, 实现COPD护理卓越标准的质量改进倡议合作(CONQUEST), that aims to improve outcomes for patients at greater risk of future COPD exacerbations by developing and implementing quality standards into routine care and measuring implementation success.

通过在各个方面应对慢性阻塞性肺病, we hope to achieve our bold ambition of cutting the COPD exacerbation rate in half by 2030 and reduce the associated cardiovascular mortality risk.

We have an investigational treatment in Phase 1 clinical trials which may provide a new approach to target fibrotic pathways earlier versus other mechanisms in development for IPF. 澳门葡京赌博游戏的豪猪抑制剂已被证明可以抑制Wnt信号传导(细胞维持的重要途径), 分化与更新), 它在IPF等疾病中非常活跃. 通过抑制目标信号通路, we hope that the novel treatment may be able to slow or prevent fibrosis in IPF and potentially other types of fibrotic diseases.


减缓或逆转疾病进展的

Slowing and ultimately reversing the progression of COPD is critical to improving the devasting outlook for patients today. We are committed to our work in this area and are investing in treatments and trials that will enable us to demonstrate true disease modification – stopping lung function decline over time and reversing the structural damage caused by the disease.

COPD is biologically complex 与 multiple disease drivers and our scientific strategy is built on our deep understanding of these pathways and the identification of novel drug targets that we can address 与 our array of new modalities. Using a precision medicine approach from the onset will mean that patients can be matched 与 the treatments they are most likely to benefit from, 打从一开始.


在新的疾病途径中追随科学

目前的治疗方法治疗症状,但不能解决慢性阻塞性肺病细胞损伤的根本原因. We are exploring approaches demonstrating disease modification through lung tissue regeneration in a number of novel inflammatory pathways:

 

白细胞介素33 (IL-33)

IL-33 is a broad-acting cytokine at the top of the inflammatory cascade that is released by the 细胞s lining the lung following 细胞 damage or stress.

IL-33是治疗多种疾病的一个有吸引力的靶点, 包括慢性阻塞性肺病, where it is hoped that inhibition of this inflammatory pathway could have the potential to deliver disease modification by addressing the IL-33-driven inflammation associated 与 tissue remodelling in the lung.3,4 IL-33在中重度COPD患者中升高,且与加重相关.

Our pre-clinical research has shown that blocking the IL-33 pathway can reduce the build-up of goblet 细胞s and mucus production back to levels seen in healthy 细胞s. 此外,IL-33是临床验证的COPD靶点3,4emerging clinical data suggesting that IL-33 blockade can improve lung function and reduce exacerbation risk in COPD.  

通过澳门葡京赌博游戏的基因组学研究中心(CGR)的倡议, we are gaining a better understanding of the potential of IL-33 as a biomarker in COPD and other chronic diseases.

髓过氧化酶(MPO)

MPO是一种已知与慢性阻塞性肺病炎症的根本原因有关的酶. 在COPD患者的气道中检测到MPO水平升高, 这两者都引发了疾病的恶化, 以及在疾病稳定状态下对肺部的持续和加速损害.5

澳门葡京赌博游戏希望抑制这种炎症途径可以在COPD中实现疾病的改变. 除了, higher circulating MPO levels are associated 与 an increased risk of adverse cardiovascular (CV) outcomes and excess death from CV-related causes,6 which is important to address since CV diseases are some of the most clinically important comorbidities in COPD.

叉头箱O4 (FOXO4)

FOXO4是一种参与细胞周期控制的转录因子, 细胞死亡和新陈代谢, 作为p53信号通路的一部分.7 暴露于慢性压力下的细胞, 比如吸烟, 是否会受到损伤,但仍能抵抗细胞死亡和肺部清除——一种被称为衰老的状态.8 当这些细胞继续存活, 它们向周围的细胞释放信号分子,从而促进进一步的损伤, 还有炎症和纤维化, 导致慢性疾病.9

We have identified a role for the FOXO4-p53 interaction in promoting 细胞ular senescence in the lung and are exploring approaches to disrupt this pathway that would initiate 细胞 death and removal of damaged 细胞s from the lung. 在澳门葡京赌博游戏早期的研究中, 澳门葡京赌博游戏发现,靶向这种相互作用创造了一个有利于肺再生的环境, 从而改善肺功能, 肺气肿造成的损伤也会减少.


转变COPD护理

澳门葡京赌博游戏追求减缓或逆转COPD疾病进展的目标, we are pushing the boundaries of science to tackle the toughest and most complex unsolved problems by targeting the underlying disease drivers and achieving greater efficacy through new modalities and novel combinations.  从一开始就采用精准医疗方法, 同时利用新工具和新技术加速进展, 意味着澳门葡京赌博游戏正在迈向一个COPD疾病改变可能成为现实的世界, 这样这些病人就可以开始过得更好, 更健康的生活. ——而且没有这种使人衰弱和危及生命的状况.


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引用:

1. 世界卫生组织. 十大死因. 可在:http://www.谁.int/news-room/fact-sheets/detail/ top-10死因[访问日期:2022年4月]

2. 阿德洛德,宋鹏,朱勇,等. 全球, 区域, 全国范围内, 风险因素, chronic obstructive pulmonary disease (COPD) in 2019: a systematic review and modelling analysis [published online ahead of print, 2022年3月10日]. 柳叶刀呼吸医学. 2022;S2213-2600(21)00511-7. doi: 10.1016/S2213-2600(21)00511-7

3. Yousuf AJ, Mohammed S, Carr L,等. Astegolimab, 一个anti-ST2, 慢性阻塞性肺疾病(COPD-ST2OP): 2a期研究, 安慰剂对照试验. 柳叶刀呼吸医学. 2022;10(5):469-477. doi: 10.1016/S2213-2600(21)00556-7

4. Rabe KF, Celli BR, wecsler ME,等. Safety and efficacy of itepekimab in patients 与 moderate-to-severe COPD: a genetic association study and randomised, 双盲, 2a期试验. 柳叶刀呼吸医学. 2021;9(11):1288-1298. doi: 10.1016/S2213-2600(21)00167-3

5. Cockayne DA, Cheng DT, Waschki B,等. 中性粒细胞炎症的系统性生物标志物, 不同疾病严重程度COPD患者的组织损伤和修复. 《澳门葡京赌博游戏》. 2012;7(6):e38629. doi: 10.1371 /杂志.玉米饼.0038629

6. 李建军,李建军,李建军,等. The relation of serum myeloperoxidase to disease progression and mortality in patients 与 chronic obstructive pulmonary disease (COPD). 《澳门葡京赌博游戏》. 2013;8(4):e61315. 出版于2013年4月18日. doi: 10.1371 /杂志.玉米饼.0061315

7.  巴尔,M. P. 等. 衰老细胞的靶向凋亡在化学毒性和衰老反应中恢复组织稳态. Cell 169, 132-147 e116, doi: 10.1016/j.细胞.2017.02.031 (2017).

8. 小屋,C. T. 等. Targeting p16-induced senescence prevents cigarette smoke-induced emphysema by promoting IGF1/Akt1 signaling in mice. 生物工程学报,2016,33 (4):391 - 391.1038/s42003-019-0532-1 (2019).

9. Tchkonia T.朱,Y.范德尔森,J.坎皮西,J. & 柯克兰J. L. 细胞衰老和衰老分泌表型:治疗机会. [J]中国医学杂志,2016,33 (5):444 - 444.1172 / JCI64098 (2013).



Veeva ID: Z4-49017
筹备日期:2022年10月