Merck gives King's College London, Wellcome Trust up to $340M in deal to develop non-opioid painkillers


2019-03-11 15:47:00 endpoint News


The hyperpolarization-activated cyclic nucleotide-gated channel comprises four members that are expressed in the heart and nervous system — and while HCN4 is well understood to modulate heart rate and drive pacemaker activity, HCN2 has emerged as a promising target for pain management. To seize the potential of inhibiting the channel to relieve pain, Merck has tied up with King’s College London, hoping the collaboration will yield a potent new class of painkillers without the dangerous side-effects seen with prescription opioids. While at the University of Cambridge Peter McNaughton discovered in 2011 the key role HCN2 plays in chronic pain — the protein can cause a continuous sensation of pain through the initiation of electrical signals in pain-sensitive nerve fibres. After moving to King’s, McNaughton conducted preclinical studies that showed blocking the activity of HCN2 in diabetic mice with neuropathic pain triggered an analgesic effect. Despite measures to reduce the use of narcotic prescription painkillers and illicit opioids in the United States, the crisis of opioid abuse, misuse and addiction is ubiquitous. In response, drugmakers are working on developing painkillers that are as potent as opioids, sans the high-risk side-effects. Under the deal with Merck $MRK, King’s and its partner Wellcome Trust are eligible to receive up to $340 million in development and sales milestones, as well as royalties if a drug is approved for use. Merck is in charge of preclinical work and conducting human trials — the trick will be to develop a drug that blocks the activity of HCN2 selectively, without disturbing HCN4, which drives the heartbeat. The US drugmaker has also pledged further funding for research into the biological mechanisms of pain at the McNaughton lab at King’s. Meanwhile the Wellcome Trust has already poured in £4.5 million to fund HCN2 research.
超极化激活的环核苷酸门控通道由4个成员组成,这些成员在心脏和神经系统中表达,而 HCN4被很好地理解为调节心率和驱动起搏器活动, HCN2已成为疼痛管理的一个有希望的目标。为了抓住抑制止痛通道的潜力,默克(Merck)公司与伦敦国王学院( King ’ s College London )建立了合作关系,希望这种合作能产生一种新的强力止痛药,而不会产生处方类阿片类药物的危险副作用。 在剑桥大学, Peter McNaughton 在2011年发现了 HCN2在慢性疼痛中的关键作用——通过在疼痛敏感的神经纤维中启动电信号,这种蛋白质可以引起持续的疼痛感觉。移至 King ’ s 后, McNaughton 进行了临床前研究,结果显示,阻断糖尿病小鼠的 HCN2活性与神经病理性疼痛触发镇痛效应。 尽管美国采取措施减少使用麻醉处方止痛药和非法阿片类药物,但阿片类药物滥用、滥用和成瘾的危机无处不在。作为回应,制药商正致力于开发与阿片类药物同样有效的止痛药,而不会产生高风险的副作用。 根据与默克公司( Merck )达成的 MRK 协议, King ’ s 及其合作伙伴 WellcomTrust 有资格获得高达3.4亿美元的开发和销售里程碑,以及一种药品获得批准使用时的使用费。默克(Merck)公司负责临床前工作和进行人体试验——关键是开发一种选择性阻断 HCN2活性的药物,而不会干扰 HCN4,从而驱动心跳。 这家美国制药商还承诺,将为金恩( King ’ s )麦克纳顿实验室( McNaughton )的疼痛生物机制研究提供更多资金。与此同时,威康信托基金已投入450万英镑,用于资助 HCN2研究。