Chen Christopher L H, Sharma Purabi Reang, Tan Boon Yeow, Low Casuarine, Venketasubramanian Narayanaswamy
Department of Pharmacology, National University of Singapore, Clinical Research Centre, Singapore.
Moleac Pte Ltd, Singapore.
Alzheimers Dement (N Y). 2019 Jan 23;5:38-45. doi: 10.1016/j.trci.2018.12.001. eCollection 2019.
Dementia is a large and growing health care burden globally, and its major cause is Alzheimer's disease (AD). MLC901 (Neuroaid II) is a simplified form of MLC601 (Neuroaid), a Traditional Chinese Medicine with neuroprotective and neuroproliferative properties in cellular and animal models of brain injury. MLC601 has been shown to modulate amyloid precursor protein (APP) processing in human neuroblastoma cell cultures and increase the levels of soluble APPα. In addition, MLC901 has been shown to reduce tau phosphorylation in vitro. Hence, MLC901 may have possible multimodal actions and a disease-modifying effect in AD. In previous clinical studies, MLC601 has shown promising effects in AD.
To investigate the safety and efficacy of MLC901 add-on therapy to standard treatment in mild-to-moderate probable AD patients stable on standard treatment and to evaluate if MLC901 has a disease-modifying effect in AD.
This is a 6-month randomized, double-blind, placebo-controlled trial in mild-to-moderate probable AD where MLC901 will be given as an add-on therapy to standard AD treatment, followed by an extension study for another 6 months, where all subjects will be treated with open-label MLC901 in addition to standard treatment. The primary outcome is safety as measured by adverse events, vital signs, electrocardiogram, laboratory tests, and physical and neurological examinations. Secondary outcomes evaluating cognition, behavior, and activities of daily living at various time points include the Alzheimer's Disease Assessment Scale-cognitive subscale, Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change, Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory, Neuropsychiatric Inventory, and Mini-Mental State Examination.
MLC901 has the potential to improve cognition in AD patients. It may also have a role in delaying disease progression. This study will be the first to provide safety and efficacy data for MLC901 in mild-to-moderate probable AD patients already receiving standard therapy.
痴呆症在全球范围内是一个巨大且不断增加的医疗负担，其主要病因是阿尔茨海默病（AD）。MLC901（Neuroaid II）是MLC601（Neuroaid）的简化形式，MLC601是一种中药，在脑损伤的细胞和动物模型中具有神经保护和神经增殖特性。MLC601已被证明可调节人神经母细胞瘤细胞培养物中淀粉样前体蛋白（APP）的加工，并提高可溶性APPα的水平。此外，MLC901已被证明在体外可减少tau蛋白磷酸化。因此，MLC901可能在AD中具有多模式作用和疾病修饰作用。在先前的临床研究中，MLC601在AD中显示出有前景的效果。
研究MLC901作为附加疗法对接受标准治疗病情稳定的轻至中度可能AD患者的安全性和疗效，并评估MLC901在AD中是否具有疾病修饰作用。
这是一项针对轻至中度可能AD患者的为期6个月的随机、双盲、安慰剂对照试验，其中MLC901将作为标准AD治疗的附加疗法给药，随后进行为期6个月的扩展研究，在此期间所有受试者除接受标准治疗外，还将接受开放标签的MLC901治疗。主要结局是通过不良事件、生命体征、心电图、实验室检查以及体格和神经学检查来衡量的安全性。评估不同时间点认知、行为和日常生活活动的次要结局包括阿尔茨海默病评估量表认知子量表、阿尔茨海默病协作研究临床总体印象变化量表、阿尔茨海默病协作研究日常生活活动量表、神经精神科问卷和简易精神状态检查表。
MLC901有改善AD患者认知的潜力。它也可能在延缓疾病进展中发挥作用。本研究将首次提供MLC901在已接受标准治疗的轻至中度可能AD患者中的安全性和疗效数据。
