Gozes Illana, Blatt Jason, Lobyntseva Alexandra
The Elton Laboratory for Molecular Neuroendocrinology, Department of Human Molecular Genetics and Biochemistry, Faculty of Medical and Health Sciences, School of Medicine, Sagol School of Neuroscience and Adams Super Center for Brain Studies, Tel Aviv University, Tel Aviv, Israel.
Transl Psychiatry. 2024 Oct 2;14(1):412. doi: 10.1038/s41398-024-03118-0.
The tauopathy inhibitor, davunetide shows sex-dependent efficacy in women suffering from progressive supranuclear palsy. Extending these findings to prodromal Alzheimer's disease, we submitted a double-blind, placebo-controlled, 12 weeks/16 weeks follow-up, davunetide clinical trial results in amnestic mild cognitive impairment (ClinicalTrials.gov ID NCT00422981), to a sex-dependent analysis.
One hundred forty-four individuals, separated into eight groups (1:2 placebo-and 2 doses, 5 mg davunetide/daily or 15 mg davunetide/twice-daily, with matching placebo intranasal volumes), were evaluated.
Significant dose-dependent cognitive increases were observed in men compared to women with a test of delayed (12 ss) visual matching to the sample. In a test of semantic working memory and attention (digit span), women showed a significant low-dose placebo effect, ensuing in a high dose significant davunetide improvement, over the matched placebo. Correlating anxiety with cognition showed sex-opposing results, with women depicting significant anxiety correlations with delayed matching to sample.
In conclusion, sex-specific prodromal Alzheimer's drug development is encouraged, with davunetide playing a lead initiative role.
tau蛋白病抑制剂达武奈肽在患有进行性核上性麻痹的女性中显示出性别依赖性疗效。为了将这些发现扩展到前驱性阿尔茨海默病,我们对一项双盲、安慰剂对照、为期12周/16周随访的达武奈肽治疗遗忘型轻度认知障碍的临床试验结果(ClinicalTrials.gov标识符NCT00422981)进行了性别依赖性分析。
对144名个体进行了评估,这些个体被分为八组(1:2的安慰剂组和两个剂量组,分别为每日5毫克达武奈肽或每日两次15毫克达武奈肽,鼻内给予的安慰剂体积与之匹配)。
在延迟(12秒)视觉样本匹配测试中,与女性相比,男性观察到显著的剂量依赖性认知能力提高。在语义工作记忆和注意力(数字广度)测试中,女性表现出显著的低剂量安慰剂效应,随后在高剂量时达武奈肽比匹配的安慰剂有显著改善。焦虑与认知的相关性显示出性别相反的结果,女性在延迟样本匹配中表现出显著的焦虑相关性。
总之,鼓励进行针对特定性别的前驱性阿尔茨海默病药物研发,达武奈肽发挥着主导作用。