MedImmune Ltd, Granta Park, Cambridge CB21 6GH, UK.
Curr Pharm Biotechnol. 2011 Oct;12(10):1660-70. doi: 10.2174/138920111798357384.
Chronic pain conditions present a huge burden on modern society. Both inflammatory and neuropathic pain are poorly treated in man; the majority of patients do not benefit from adequate pain relief, and side effects of currently used treatments are common. Discovery and development of novel therapies remains an imperative, but the ability to genuinely test the efficacy of novel therapies is often limited by effects at targets other than intended, particularly with novel small molecule approaches. Approaches which limit these off-target activities, and thus avoid the commonest cause of terminating development of new therapeutics may provide a greater ability to genuinely test targets of choice clinically, and here, biologic therapeutics provide such an opportunity; in the major class of biologic therapies, monoclonal antibodies, inherent exquisite selectivity is intrinsic to their nature. Antibody therapeutics have been developed successfully in the immunology and cancer fields, and recent progress in analgesia suggests that these therapeutics may transform treatment paradigms in a similar manner to that observed within, for example, the rheumatoid arthritis space. In addition, opportunities with other biologic approaches, such as peptides, further broadens the potential to bring forward genuinely novel approaches to pain. In this review, the current status of biologic therapies, as well as future opportunities are reviewed.
慢性疼痛状况给现代社会带来了巨大的负担。无论是炎症性疼痛还是神经性疼痛,在人类中都难以得到有效治疗;大多数患者无法从充分的疼痛缓解中受益,而且目前使用的治疗方法的副作用很常见。因此,发现和开发新型疗法仍然是当务之急,但新型疗法的疗效的真正测试能力往往受到除预期靶点以外的靶点的影响,特别是对于新型小分子方法。那些限制这些非靶点活性的方法,从而避免了新型治疗药物开发中最常见的终止原因,可能会提供更大的能力来真正在临床上测试选择的靶点,而在这里,生物疗法提供了这样的机会;在生物疗法的主要类别——单克隆抗体中,固有的高度选择性是其本质属性。抗体疗法已在免疫学和癌症领域成功开发,而最近在镇痛方面的进展表明,这些疗法可能会以类似于在类风湿关节炎领域观察到的方式改变治疗模式。此外,其他生物方法的机会,如肽,进一步扩大了将真正新颖的疼痛治疗方法推向前进的潜力。在这篇综述中,回顾了生物疗法的现状以及未来的机会。