Institute of Clinical Sciences, Lund University, Lund, Sweden.
Headache. 2018 May;58 Suppl 1:33-47. doi: 10.1111/head.13305.
The neuropeptide calcitonin gene-related peptide is well established as a key player in the pathogenesis of migraine. Clinical studies show calcitonin gene-related peptide levels correlate with migraine attacks, and decreases in this neuropeptide can indicate antimigraine therapy effectiveness. Research has revealed a wide distribution of expression sites for calcitonin gene-related peptide in the central and peripheral nervous system. Of these, the calcitonin gene-related peptide receptor, which binds calcitonin gene-related peptide with high affinity, has attracted growing interest as a viable target for antimigraine therapies. An incentive to pursue such research is the continuing unmet medical need of patients. Triptans have offered some clinical benefit, but many patients do not respond and these drugs have important safety considerations. Initial calcitonin gene-related peptide-focused research led to development of the "gepant" small-molecule calcitonin gene-related peptide receptor blockers. Positive efficacy reports concerning the gepants have been tempered by safety findings which led to the discontinuation of some of these agents. Currently, there is considerable excitement regarding monoclonal antibodies against calcitonin gene-related peptide (eptinezumab, galcanezumab, fremanezumab) and the calcitonin gene-related peptide receptor (erenumab). To date, these monoclonal antibodies have shown promising efficacy in clinical trials, with no major safety concerns. If ongoing long-term studies show that their efficacy can be maintained, this may herald a new era for effective antimigraine therapies.
降钙素基因相关肽是偏头痛发病机制中的关键因子，这一点已得到充分证实。临床研究表明，降钙素基因相关肽水平与偏头痛发作相关，该神经肽的减少可表明偏头痛治疗的有效性。研究揭示了降钙素基因相关肽在中枢和外周神经系统中有广泛的表达部位。其中，与降钙素基因相关肽具有高亲和力结合的降钙素基因相关肽受体作为一种可行的偏头痛治疗靶点，引起了越来越多的关注。推动这方面研究的一个动力是患者持续存在的未满足的医疗需求。曲普坦类药物提供了一些临床益处，但许多患者没有反应，而且这些药物存在重要的安全问题。最初针对降钙素基因相关肽的研究导致了“ gepant”小分子降钙素基因相关肽受体阻滞剂的开发。关于 gepants 的积极疗效报告受到安全性发现的影响，导致其中一些药物被停用。目前，针对降钙素基因相关肽（依替尼单抗、加兰他敏、氟雷马尼单抗）和降钙素基因相关肽受体（erenumab）的单克隆抗体引起了极大的关注。迄今为止，这些单克隆抗体在临床试验中表现出了有希望的疗效，且没有出现重大安全问题。如果正在进行的长期研究表明其疗效能够维持，这可能预示着有效的偏头痛治疗新时代的到来。
