Abstract：
UNASSIGNED: Alzheimer\'s disease (AD) is a neurodegenerative condition characterized by progressive cognitive deterioration, functional impairments, and neuropsychiatric symptoms. Valiltramiprosate is a tramiprosate prodrug being investigated as a novel treatment for AD.
UNASSIGNED: The online databases PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched using the terms \'ALZ-801\' or \'valiltramiprosate.\' Alzheon press releases were reviewed for emerging clinical information. Valiltramiprosate is an oral, well-tolerated synthetic valine-conjugate prodrug of tramiprosate. Valiltramiprosate\'s active metabolite include tramiprosate and 3-sulfopropanoic acid. Proposed mechanism of action is multiligand binding to Aβ42 which stabilizes amyloid monomers to prevent peptide aggregation and oligomerization. Pharmacokinetic studies show 52% oral bioavailability, rapid absorption, approximately 40% brain-drug exposure, and near complete renal clearance. Compared to tramiprosate, valiltramiprosate extends plasma tramiprosate half-life and improves interindividual pharmacokinetic variability. Interim analyses from valiltramiprosate\'s phase II biomarker trial show: (1) significant reductions in plasma p-tau181 and related AD fluid biomarkers; (2) brain structure preservation and reduced hippocampal atrophy by MRI; and (3) improvements on cognitive assessments at multiple timepoints. Its phase III clinical trial in ApoE ε4 homozygotes is near completion.
UNASSIGNED: Valiltramiprosate\'s clinical trial data show early indications of efficacy with potential disease modifying effect in AD.
UNASSIGNED: The online databases PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched using the terms \'ALZ-801\' or \'valiltramiprosate.\' Alzheon press releases were reviewed for emerging clinical information. Valiltramiprosate is an oral, well-tolerated synthetic valine-conjugate prodrug of tramiprosate. Valiltramiprosate\'s active metabolite include tramiprosate and 3-sulfopropanoic acid. Proposed mechanism of action is multiligand binding to Aβ42 which stabilizes amyloid monomers to prevent peptide aggregation and oligomerization. Pharmacokinetic studies show 52% oral bioavailability, rapid absorption, approximately 40% brain-drug exposure, and near complete renal clearance. Compared to tramiprosate, valiltramiprosate extends plasma tramiprosate half-life and improves interindividual pharmacokinetic variability. Interim analyses from valiltramiprosate\'s phase II biomarker trial show: (1) significant reductions in plasma p-tau181 and related AD fluid biomarkers; (2) brain structure preservation and reduced hippocampal atrophy by MRI; and (3) improvements on cognitive assessments at multiple timepoints. Its phase III clinical trial in ApoE ε4 homozygotes is near completion.
UNASSIGNED: Valiltramiprosate\'s clinical trial data show early indications of efficacy with potential disease modifying effect in AD.
摘要：
■阿尔茨海默病（AD）是一种神经退行性疾病，其特征是进行性认知恶化，功能障碍，神经精神症状.Valiltramipacate是一种正在研究的曲米酸前药，作为AD的新型治疗方法。
■在线数据库PubMed，Embase,WebofScience,科克伦图书馆,和ClinicalTrials.gov使用术语\'ALZ-801\'或\'valiltramiprosate进行搜索。对Alzheon新闻稿进行了审查，了解新出现的临床信息。Valiltramiprosate是一种口服，耐受性良好的合成缬氨酸-曲米酸偶联前药。Valiltramipacate的活性代谢产物包括tramipacate和3-磺基丙酸。提出的作用机制是多配体与Aβ42结合,其稳定淀粉样蛋白单体以防止肽聚集和寡聚化。药代动力学研究显示52％的口服生物利用度，快速吸收,大约40%的脑内药物暴露,接近完全肾清除.与曲米普酸相比，伐拉米酸延长了血浆曲米酸的半衰期，并改善了个体间的药代动力学变异性。来自伐拉米酸的II期生物标志物试验的中期分析显示：（1）血浆p-tau181和相关AD流体生物标志物的显着减少；（2）通过MRI保留脑结构并减少海马萎缩；（3）在多个时间点的认知评估方面的改善。ApoEε4纯合子的III期临床试验已接近完成。
■Valiltramiprosate的临床试验数据显示，在AD中具有潜在的疾病改善作用的早期疗效。
■在线数据库PubMed，Embase,WebofScience,科克伦图书馆,和ClinicalTrials.gov使用术语\'ALZ-801\'或\'valiltramiprosate进行搜索。对Alzheon新闻稿进行了审查，了解新出现的临床信息。Valiltramiprosate是一种口服，耐受性良好的合成缬氨酸-曲米酸偶联前药。Valiltramipacate的活性代谢产物包括tramipacate和3-磺基丙酸。提出的作用机制是多配体与Aβ42结合,其稳定淀粉样蛋白单体以防止肽聚集和寡聚化。药代动力学研究显示52％的口服生物利用度，快速吸收,大约40%的脑内药物暴露,接近完全肾清除.与曲米普酸相比，伐拉米酸延长了血浆曲米酸的半衰期，并改善了个体间的药代动力学变异性。来自伐拉米酸的II期生物标志物试验的中期分析显示：（1）血浆p-tau181和相关AD流体生物标志物的显着减少；（2）通过MRI保留脑结构并减少海马萎缩；（3）在多个时间点的认知评估方面的改善。ApoEε4纯合子的III期临床试验已接近完成。
■Valiltramiprosate的临床试验数据显示，在AD中具有潜在的疾病改善作用的早期疗效。
