| 查看: 91 | 回复: 0 | |||
| 当前主题已经存档。 | |||
[交流]
疗效更持久的新型抗关节炎药物
|
|||
|
疗效更持久的新型抗关节炎药物 http://www.dxy.cn/bbs/post/view? ... 1&tpg=1&age New engineered drug may offer prolonged arthritis relief 一种能够更长时间缓解关节炎疼痛的新药. DURHAM, N.C. -- Researchers at Duke University have devised a new way to significantly prolong the effects of an anti-inflammatory drug, potentially making it useful for providing longer-lasting treatment for osteoarthritis, the most common form of arthritis. Duke University的研究人员发明了一种新的够显著延长抗炎药物作用的药物，在骨关节炎（最为常见的关节炎）治疗方面具有潜在用途。 The modified drug, which would be injected directly into arthritic joints, could last for several weeks rather than just the few hours the unmodified drug would last, the researchers said. 研究人员称经过改良的药物可以直接注射入患病关节，药效可持续数周，而原型药物仅能维持几小时。 In their study, the researchers modified a drug called interleukin-1 receptor antagonist (IL1RA). They found that the drug, which is a protein, could be improved by attaching a second protein that clumps together at normal body temperatures. The combined drug likewise would assemble into clumps in the body to serve as "drug depots" that gradually release active drug particles, the researchers said. 在研究中，研究人员改良了IL-1受体拮抗剂。他们在IL-1受体拮抗剂上链接了一个亚蛋白，这种亚蛋白在正常体温下成簇存在。“这种混合药物同样将会在体内成簇存在，犹如“药物储藏室”，逐渐释放药效。”研究人员说。 "Although the conventional drug is being used for autoimmune diseases, no one yet knows how much of it would be needed to achieve a therapeutic effect for osteoarthritis," said Lori Setton, associate（副的） professor of biomedical engineering and surgery. "Current estimates suggest it would require perhaps two injections per week of the unmodified drug. “尽管原型药物已经在用于治疗自身免疫性疾病，但是没人知道治疗骨关节炎的最佳用量”Lori Setton（生物医学工程和外科教授）说，“目前建议每周注射两次。” "With this advance, we believe treatments could go from twice a week to perhaps twice a month, and that would be a huge clinical gain," she said. “就新药来说，我们相信用法会从每周两次开始甚至能达到每月两次，这在临床上有很大的价值。”她说。 By remaining at the site of disease, the drug also might cause fewer negative side effects than the unmodified drug, the researchers added. 这种新药长期使用比原型药副作用更小，研究者称。 The team reported an initial proof-of-concept study假设证实研究 on Saturday, Oct. 14, at the Biomedical Engineering Society annual meeting, in Chicago. The team also has reported related findings online in the Journal of Controlled Release. 研究团队于十月14日周六的在芝加哥he Biomedical Engineering Society年会上公布了他们的一项最初的假设证实研究，同时也联机在 the Journal of Controlled Release.公布了他们的相关研究。 The work was supported by a Coulter Foundation Translational Research Partnership award to the biomedical engineering department at Duke's Pratt School of Engineering, and by the National Institutes of Health and a United Negro College Fund-Merck graduate dissertation fellowship. 研究的赞助者（省略未翻译）。 Osteoarthritis is a degenerative joint disease that affects an estimated 21 million adults in the United States. It is the nation's most prevalent musculoskeletal disorder and the leading cause of disability, the researchers said, adding that as the average age of the population continues to rise, the incidence of osteoarthritis will increase. " 骨关节炎是一种关节退行变，在美国估计有2.1亿患病，是最普遍的肌肉骨骼异常的致残原因，研究者说，随着老年人口的增多，骨关节炎亦将增多。 Osteoarthritis had been attributed primarily to the gradual wear and tear of joint surfaces. More recently, however, scientists have discovered that inflammation sparked by the immune system also plays an important role in the worsening of the disease. . 关节炎一直被认为由于关节表面的逐渐磨损断裂引起。最近，科学家发现免疫系统引起的炎症在病情恶化中起重要作用。 Specifically, scientists have linked a key molecule involved in inflammation, called interleukin-1 (IL-1), to osteoarthritis. IL-1 heightens the activity of enzymes that damage joints by breaking down their collagen "framework," Setton explained. She credits team member Virginia Kraus, professor of rheumatology and immunology at Duke University Medical Center, for focusing on IL-1 as a major mediator of osteoarthritis in the joint. 科学家们将炎症中的关键分子IL-1与骨关节炎相联系。IL-1可以通过破坏骨胶原框架来提高损伤关节的酶的作用，Setton解释。她赞同团队成员Virginia Krau（ Duke University Medical Center风湿病和免疫学教授）关注IL-1作为骨关节炎中主要介质。 Given the immune system's suspected role in osteoarthritis, scientists have suspected that the interleukin-1 receptor antagonist drug, which is known to block IL-1 activity, might have value in diminishing the severity of osteoarthritis, said Mohammed Shamji, a neurosurgery resident pursuing his Ph.D. in Setton's laboratory. 鉴于免疫系统在骨关节炎中的疑似作用，科学家们猜想IL-1受体拮抗剂在减轻骨关节炎严重性方面会有作用，Mohammed Shamj说（Setton's实验室博士研究生） However, trials of IL1RA for osteoarthritis have had limited success, primarily because the drug tends to break down quickly, according to the researchers. 然而IL-1受体拮抗剂治疗骨关节炎的临床实验仅取得有限成功，研究人员认为主要是因为药物代谢太快。 "Physicians can inject large amounts of this drug systemically, but it's cleared very rapidly and there is no evidence that it reaches the joint space," said Helawe Betre, who performed these studies for his doctoral work at Duke and now works at Zimmer Orthobiologics. "We set out to develop a modified version of the drug that when injected directly might stay in the joint long enough to be effective." “医生们给病人大计量注射IL-2受体拮抗剂，然而它代谢很快并且也不知是否能到达关节，”Helawe Betre说，“我们开始研究一种改进型的药物，这种药物能够直接注射入关节并且存在足够长时间。 To build in such durability, Betre turned to a class of proteins called elastin-like polypeptides (ELPs). Once ELPs in solution reach a certain threshold temperature, they assemble into protein aggregates. Study collaborator Ashutosh Chilkoti, a professor of biomedical engineering at the Pratt School, previously had investigated the use of ELPs that clump at temperatures higher than normal body temperature for treating cancers. 为了达到持久疗效，Beter开始关注一种叫做弹性多肽的蛋白质（ELPs）。当这种蛋白质达到阈温度时，便会聚集成聚合体。研究合作者Ashutosh Chilkoti（Pratt School生物医学工程教授）曾经研究过ELPs在癌症治疗中的研究，ELPs聚集的温度高于正常体温。 ELPs aren't recognized by the body's immune system as foreign substances, and thus they have some unique advantages for biomedical applications, according to the researchers. Also, ELPs can be joined directly to genes that control the production of various proteins in cells, with the combination forming "fusion proteins." As the proteins degrade, they yield simple amino acids, which are the building blocks of all proteins. 据研究者称，ELPs不引起免疫反应所以它在生物医学中有独特的优点。ELPs可以直接与细胞内产生各种蛋白产物的基因相结合，从而形成“融合蛋白”。 By experimenting with composition, molecular weight and concentration of various ELPs, Betre developed a protein for use in joints that would precipitate out of solution and clump at normal body temperature. 通过对各种ELPs的组成、分子量和浓度，Betre研制出一种用于关节的蛋白，它能在正常体温下从溶液中聚集沉淀。 When he injected the sticky ELP into the knees of rats, the protein proved to have a 25-fold longer half-life in the joint than a similar soluble protein, Betre reported in the journal article. Half-life is the time required for half the quantity of the protein to be broken down and eliminated from the joint space. 当他把粘性ELP注射入小鼠膝关节，在关节中这种蛋白的半衰期是相似的可溶性蛋白的25倍，Betre报道说。半衰期指一半蛋白从关节腔中分解和消失用的时间。 "At 12 hours, the soluble protein was already at a concentration in the joint below 10 percent of the injected dose," Setton said. Setton说“12小时后，可溶性蛋白在关节中的浓度低于注射量的10%。” In contrast, the sticky ELP took about two weeks to fall to the 10 percent level in the animals' joints -- a "really substantial increase," she said. 相比之下，粘性ELP在动物关节中大约2周后才降至10%—“显著延长”，她说。 Moreover, rats injected with the clumping ELP contained lower blood levels of the protein, suggesting that a protein drug paired to the ELP might also have the benefit of fewer side effects, Shamji said. This would be important, he said, because IL1RA can weaken the immune system and make patients more susceptible to infection. 更重要的是，注射聚集ELP的小鼠血中含有的蛋白更少，表明它的副作用更少，Shamji说。这将很重要，他说，因为IL-1受体拮抗剂会降低免疫功能使得病人易被感染。 Such vulnerability to infection is a particular problem for patients treated for chronic diseases such as osteoarthritis, and this vulnerability suggests the need for a local treatment, Shamji added. 这种副作用在慢性疾病如骨关节炎的治疗中更加明显，进而需求局部用药，Shamji进一步指出。 Based on the initial investigation, the team paired the ELP with the IL1RA drug in a second study, to test whether the fusion protein would retain the ability to suppress IL-1 activity and fight inflammation. 基于初步研究，该团队在接下来的研究中，将ELP和IL-1拮抗剂相比较，以验证融合蛋白仍然可以抑制IL-1的活性和抗炎。 The researchers treated human white blood cells with either the original or the modified drug. White blood cells are responsible for mounting the body's immune response and normally react to IL-1 by growing in numbers and releasing molecules that further activate the immune system. Active IL1RA therefore serves to dampen the immune cells' rate of proliferation, Shamji said. 研究者分别用原型和改良后的药物处理人白细胞。白细胞能够发动机体免疫反应而起一般通过数目增加和释放进一步激活免疫系统的分子对IL-1做出反应。 White blood cells treated with the modified drug increased in number at a slower than normal pace, evidence of the drug's activity, Shamji reported at the Biomedical Engineering Society meeting. But its potency dropped by a factor of about 20（大约20%的比率） compared to the pure drug. 用新药处理过的白细胞增长速度减慢是新药有效的证据，Shamji在the Biomedical Engineering Society会议上报告，但是与原型药物相比潜能下降大约20%. Further studies, however, suggested the fusion protein might do better in an arthritic joint, Shamji said. The researchers were surprised to find that the same inflammatory enzymes that destroy joint collagen also chew ELP from the original drug protein, thereby restoring its activity. 尽管如此，进一步的研究提示融合蛋白在病变关节内可能更有效Shamji说。研究人员惊奇地发现破坏关节中骨胶原的酶同样会使原型药物从ELP中分离出来而且分离后仍有作用。 "With the ELP tag gone, you get back yor originally active drug," Shamji said “ELP去了，原型归来”Shamji说 "That finding was pretty unexpected," Setton added. "We hadn't intentionally designe d it to have that feature at all. "这太意外了，完全出乎我们的意料。 The researchers now plan to work with collaborators to test the modified drug's ability to interfere with the progression of disease in the joints 研究人员将进一步测试新药在病程中的作用。 |
回复此楼» 猜你喜欢
335求调剂
已经有0人回复
-
AUTODOCK GPU 使用报错
已经有0人回复
-
眼科学论文润色/翻译怎么收费?
已经有242人回复
-
100205精神病与精神卫生学，初试317，西医综合224，英语34，求助B区调剂机会
已经有1人回复
» 本主题相关商家推荐: (我也要在这里推广)
