کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5824208 | 1118440 | 2011 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The increasing challenge of discovering asthma drugs
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کلمات کلیدی
FEV1CysLTSABAAQLQT helper cell type 2Th2PEFRFDAICSTLRGPCRACQCysteinyl leukotrienesTGFβAHRSRS-AIgETNFmRNAAtopy - آتوپی IgE, immunoglobulin E - ایمونوگلوبولین Einterleukin - اینترلوکینBALF - بافتDizygotic - بیضویTransforming growth factor β - تبدیل فاکتور رشد βToll-like receptor - تیالآرpeak expiratory flow rate - حداکثر سرعت جریان انعقادیmessenger ribonucleic acid - رسوب ریبونوکلئیک اسیدFood and Drug Administration - سازمان غذا و داروLABA - سودtumor necrosis factor - فاکتور نکروز تومورasthma phenotypes - فنوتیپ های آسمLar - لارBronchoalveolar lavage fluid - مایع لارو برونکلوفلورforced expiratory volume in 1 second - مجاز خروج مجدد در 1 ثانیهMonozygotic - مونوزیگوتmillion - میلیونSMART - هوشمندانهEarly airway response - پاسخ اولیه هواپیماairway hyper-responsiveness - پاسخ سریع هواپیماLate asthmatic response - پاسخ کوتاه مدت آسمAsthma Control Questionnaire - پرسشنامه کنترل آسمasthma quality-of-life questionnaire - پرسشنامه کیفیت زندگی آسمSingle nucleotide polymorphism - پلیمورفیسم تک نوکلئوتیدیSNP - چندریختی تک-نوکلئوتیدasthma genetics - ژنتیک آسمInhaled corticosteroid - کورتیکواستروئیدهای استنشاقیEAR - گوشG protein-coupled receptor - گیرندههای جفتشونده با پروتئین جی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The prevalence of asthma continues to rise. Current drugs provide symptomatic relief to some, but not all, patients. Despite the need for new therapeutics, and a huge research effort, only four novel agents from two classes of drugs - the antileukotrienes and an anti-IgE antibody - have been approved in the last 30 years. This review highlights three particular issues that contribute to the challenge of identifying new therapeutics. First is an over-reliance on animal models of allergy to define targets and expectations of efficacy that has met with poor translation to the clinical setting. While sensitivity to particular aeroallergens is one key risk factor for asthma, atopy and asthma are not synonymous, and while about half of adult asthmatics are atopic the incidence of allergic asthma is probably <50%. The second issue is a fundamental disconnect between the directions of basic research and clinical research. Basic research has developed a detailed, reductive, unifying mechanism of antigen-induced, T helper type 2 cell-mediated airway inflammation as the root cause of asthma. In contrast, clinical research has started to identify multiple asthma phenotypes with differing cellular components, mediators and sensitivities to asthma drugs, and probably varying underlying factors including susceptibility genes. Finally, different features of asthma - bronchoconstriction, symptoms, and exacerbations - respond diversely to treatment; effects that are not captured in animal models which do not develop asthma per se, but utilize unvalidated surrogate markers. Basic research needs to better integrate and utilize the clinical research findings to improve its relevance to drug discovery efforts.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 82, Issue 6, 15 September 2011, Pages 586-599
Journal: Biochemical Pharmacology - Volume 82, Issue 6, 15 September 2011, Pages 586-599
نویسندگان
Kevin Mullane,