Williams-Beuren syndrome (WBS) is a rare disorder that causes hyper-social behavior, intellectual disability, memory problems, and life-threatening overgrowth of the heart. Behavioral therapies can help improve the cognitive and social aspects of the syndrome and surgery is sometimes used to treat the effects on the heart, although often with limited success. However, there are currently no medications available to treat WBS. The endocannabinoid system – which consists of cannabis-like chemical messengers that bind to specific cannabinoid receptor proteins – has been shown to influence cognitive and social behaviors, as well as certain functions of the heart. This has led scientists to suspect that the endocannabinoid system may play a role in WBS, and drugs modifying this network of chemical messengers could help treat the rare condition. To investigate, Navarro-Romero, Galera-López et al. studied mice which had the same genetic deletion found in patients with WBS. Similar to humans, the male mice displayed hyper-social behaviors, had memory deficits and enlarged hearts. Navarro-Romero, Galera-López et al. found that these mutant mice also had differences in the function of the receptor protein cannabinoid type-1 (CB1). The genetically modified mice were then treated with an experimental drug called JZL184 that blocks the breakdown of endocannabinoids which bind to the CB1 receptor. This normalized the number and function of receptors in the brains of the WBS mice, and reduced their social and memory symptoms. The treatment also restored the animals’ heart cells to a more normal size, improved the function of their heart tissue, and led to lower blood pressure. Further experiments revealed that the drug caused the mutant mice to activate many genes in their heart muscle cells to the same level as normal, healthy mice. These findings suggest that JZL184 or other drugs targeting the endocannabinoid system may help ease the symptoms associated with WBS. More studies are needed to test the drug’s effectiveness in humans with this syndrome. Furthermore, the dramatic effect JZL184 has on the heart suggests that it might also help treat high blood pressure or conditions that cause the overgrowth of heart cells.
威廉姆斯-贝伦综合征(WBS)是一种罕见的疾病,会导致超社会行为,智力残疾,记忆问题,和危及生命的心脏过度生长。行为疗法可以帮助改善综合症的认知和社会方面,有时手术用于治疗对心脏的影响,虽然通常成功有限。然而,目前尚无可用于治疗WBS的药物.内源性大麻素系统-由与特定大麻素受体蛋白结合的大麻样化学信使组成-已被证明会影响认知和社会行为,以及心脏的某些功能。这导致科学家怀疑内源性大麻素系统可能在WBS中起作用,改变这种化学信使网络的药物可以帮助治疗这种罕见的疾病。为了调查,纳瓦罗-罗梅罗,Galera-López等人。研究了在WBS患者中发现的具有相同遗传缺失的小鼠。和人类一样,雄性小鼠表现出超社会行为,有记忆缺陷和扩大的心脏。纳瓦罗-罗梅罗,Galera-López等人。发现这些突变小鼠在受体蛋白大麻素1型(CB1)的功能上也存在差异。然后用称为JZL184的实验药物治疗转基因小鼠,该药物阻断与CB1受体结合的内源性大麻素的分解。这使WBS小鼠大脑中受体的数量和功能正常化,减少了他们的社交和记忆症状。治疗还使动物的心脏细胞恢复到更正常的大小,改善了心脏组织的功能,导致血压降低.进一步的实验表明,该药物使突变小鼠的心肌细胞中的许多基因激活到与正常水平相同的水平,健康的老鼠这些发现表明,JZL184或其他靶向内源性大麻素系统的药物可能有助于缓解与WBS相关的症状。需要更多的研究来测试这种药物在患有这种综合症的人类中的有效性。此外,JZL184对心脏的巨大影响表明,它也可能有助于治疗高血压或导致心脏细胞过度生长的疾病。