A Phase III, 26-Week, Double-blind, Randomised, Placebo-controlled, Parallel-group Study to Investigate the Efficacy and Safety of Daily Administration of Tricaprilin in Subjects With Mild to Moderately Severe Probable Alzheimer's Disease

The purpose of this study is to evaluate the effects of tricaprilin (20 g twice a day) on cognition, activities of daily living, resource utilisation, safety and tolerability, in subjects with mild to moderately severe probable AD.
This is a randomised, double-blind, placebo-controlled, parallel-group, multi-centre design in up to 535 participants.

开始日期2025-01-01

申办/合作机构

Cerecin, Inc.

NCT05628636 / Completed临床1期

A Phase 1, Open-label Study to Evaluate the Tolerability of 21 Days of Treatment With the AC-OLE-01-VA Formulation of Tricaprilin Under Different Dosing Conditions in Healthy Participants

This is an open-label, 3-arm study to compare tolerability of three different titration and dosing schedules of the AC-OLE-01-VA formulation of tricaprilin.
Following a screening of up to 28 days, eligible participants will be initially randomised to one of 2 arms (Arm 1 or Arm 2). Arms 1 and 2 will be completed in advance of Arm 3 with all subsequent participants allocated to Arm 3.

开始日期2022-11-14

申办/合作机构

Cerecin, Inc.

NCT05408780 / Completed临床1期

A Phase 1, Two-part, Randomized Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of a Liquid Formulation of Tricaprilin, and Matching Placebo to Include Single-dose and Food Effect (Part A), and Titration Tolerability (Part B), in Healthy Subjects

The purpose of this study is to evaluate the PK, safety, and tolerability of a new liquid formulation of tricaprilin.

开始日期2022-07-14

申办/合作机构

Cerecin, Inc.

100 项与三辛酸甘油酯相关的临床结果

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100 项与三辛酸甘油酯相关的转化医学

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100 项与三辛酸甘油酯相关的专利（医药）

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项与三辛酸甘油酯相关的文献（医药）

2024-02-01·Poultry science

Inclusion of trans-cinnamaldehyde and caprylic acid in feed results in detectable concentrations in the chicken gut and reduces foodborne pathogen carriage

Article

作者: Liyanage, Rohana ; Assumpcao, Anna L Facchetti V ; Donoghue, Annie M ; Arsi, Komala ; Jesudhasan, Palmy R R ; Caputi, Valentina ; Lyte, Joshua M

Poultry act as a major reservoir host for Salmonella and Campylobacter spp., the 2 leading causes of foodborne illnesses globally and in the United States. Preharvest stage interventions to reduce foodborne pathogen carriage in poultry are increasingly informed by consumer preference for antibiotic-free poultry production. The in-feed inclusion of plant-derived antimicrobial compounds is a promising antibiotic alternative strategy to reduce foodborne pathogen load in the broiler chicken gut. Yet, the fate of these phytochemicals through the broiler chicken gastrointestinal tract is unknown. Likewise, while in-feed phytochemicals have been widely demonstrated in challenge models to reduce foodborne pathogen carriage, little is known regarding efficacy to curb natural routes of infection. As such, the aim of the present study was 2-fold. We sought to determine the concentrations of 2 phytochemicals, trans-cinnamaldehyde and caprylic acid, in each region of the chicken gastrointestinal tract following their in-feed inclusion over a 6-wk production period. In addition, we investigated how the in-feed provision of these phytochemicals may protect against environmental acquisition of Campylobacter jejuni and Salmonella spp. Trans-cinnamaldehyde and caprylic acid were detected in crop, gizzard, duodenal, jejunal, and ileal contents. Crop and gizzard concentrations were not significantly (P > 0.05) different. A significant (P < 0.05) decrease in phytochemical concentration was observed in intestinal regions compared to crop and gizzard. Trans-cinnamaldehyde was consistently identified in cecal and colon contents, while caprylic acid was not detectable in these regions. Trans-cinnamaldehyde and caprylic acid were found to reduce (P < 0.05) Salmonella load. Together, our data establish that the in-feed addition of trans-cinnamaldehyde and caprylic acid, 2 phytochemicals that have previously been shown to exert antimicrobial activity against poultry-associated foodborne pathogens, results in detectable concentrations in the broiler chicken gastrointestinal tract. By providing researchers with a gastrointestinal region-by-region map of phytochemical concentrations, the present study is expected to inform the choice of in-feed phytochemicals targeting foodborne pathogen carriage in the broiler chicken gastrointestinal tract.

2024-01-01·European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences

Nanostructured lipid carriers loaded into in situ gels for breast cancer local treatment

Article

作者: Lopes, Luciana B ; Martins, Tereza S ; Passos, Julia S ; Ishida, Kelly ; Apolinario, Alexsandra C

In this study, nanostructured lipid carriers (NLC) were developed and employed to obtain in situ thermosensitive formulations for the ductal administration and prolonged retention of drugs as a new strategy for breast cancer local treatment. NLC size was influenced by the type and concentration of the oil phase, surfactants, and drug incorporation, ranging from 221.6 to 467.5 nm. The type of liquid lipid influenced paclitaxel and 5-fluorouracil cytotoxicity, with tributyrin-containing NLC reducing IC₅₀ values by 2.0-7.0-fold compared to tricaprylin NLC in MCF-7, T-47D and MDA-MB-231 cells. In spheroids, the NLCs reduced IC₅₀ compared to either drug solution (3.2-6.2-fold). Although a significant reduction (1.26 points, p < 0.001) on the health index of Galleria mellonella larvae was observed 5 days after NLC administration, survival was not significantly reduced. To produce thermosensitive gels, the NLCs were incorporated in a poloxamer (11 %, w/w) dispersion, which gained viscosity (2-fold) at 37 °C. After 24 h, ∼53 % of paclitaxel and 83 % of 5-fluorouracil were released from the NLC; incorporation in the poloxamer gel further prolonged release. Intraductal administration of NLC-loaded gel increased the permanence of hydrophilic (2.2-3.0-fold) and lipophilic (2.1-2.3-fold) fluorescent markers in the mammary tissue compared to the NLC (as dispersion) and the markers solutions. In conclusion, these results contribute to improving our understanding of nanocarrier design with increased cytotoxicity and prolonged retention for the intraductal route. Tributyrin incorporation increased the cytotoxicity of paclitaxel and 5-fluorouracil in monolayer and spheroids, while NLC incorporation in thermosensitive gels prolonged tissue retention of both hydrophilic and hydrophobic compounds.

2023-12-01·Applied nursing research : ANR

Ketogenic therapies in Parkinson's disease, Alzheimer's disease, and mild cognitive impairment: An integrative review

Review

作者: Price, Susan ; Ruppar, Todd M

BACKGROUND:

Ketogenic therapies have shown benefit for seizure reduction in epilepsy but their impact on other neurologic conditions is less known. In this literature review, the efficacy of ketogenic therapies were assessed in Parkinson's disease (PD), Alzheimer's disease (AD), and mild cognitive impairment (MCI).

METHODS:

A literature search was conducted using PubMed, Scopus, and Google Scholar focusing on ketogenic therapies in PD, AD, and MCI.

RESULTS:

A total of 2565 records were identified with a total of 15 studies (3 for PD and 12 for MCI/AD) meeting criteria for analysis. The ketogenic diet was used in all the PD studies and did show significant improvement in motor function either through vocal quality, gait, freezing, tremor, and/or balance. A variety of ketogenic therapies were utilized in the MCI and AD groups including a ketogenic diet, low-carbohydrate diet, modified Adkins diet, Mediterranean diet with coconut oil supplementation, a ketogenic diet with a ketogenic medium chain triglyceride (kMCT) supplement, as well as ketogenic supplements including a ketogenic drink with kMCT, oral ketogenic compounds (Axona and AC-1202), and MCT oil or emulsion. The ketogenic diet independently showed a non-significant trend towards improvement in cognition. The Mediterranean diet, modified Adkins diet, and low-carbohydrate diet showed statistically significant improvements in some, although not all, of their cognitive measures. Use of ketogenic supplements, drinks, or compounds showed variable results in the AD and MCI groups. The Axona and AC-1202 compounds showed no significant improvement in cognition at the end of their respective 90-day trials. Most MCT supplements did show cognitive improvements, although only after 6 months of adherence. Adherence to the intervention was problematic in most of the diet studies.

CONCLUSION:

Ketogenic therapies have promise in PD, AD, and MCI for symptom improvement although larger studies are needed to support their implementation in clinical practice.

项与三辛酸甘油酯相关的新闻（医药）

2024-03-21

·蒲公英Ouryao

药典委：11个辅料标准草案公示

转自：国家药典委编辑：水晶3月21日，国家药典委公示了11个辅料标准草案。11个标准草案：预胶化淀粉、玉米淀粉、豌豆淀粉、木薯淀粉、麦芽糊精、马铃薯淀粉、小麦淀粉、果胶、三辛酸甘油酯、抗坏血酸棕榈酸酯、可溶性淀粉。预胶化淀粉、玉米淀粉、豌豆淀粉、木薯淀粉、马铃薯淀粉5个标准：删去“重金属” 项。麦芽糊精，删去“重金属” 项和“砷盐”项。小麦淀粉：删除“总蛋白”项下非蛋白氮含量，删去“重金属” 项。果胶：修订CAS号、来源与制法及含量限度、薄层鉴别、检查、类别、标示6项内容。三辛酸甘油酯：修订结构式、CAS号、分子式和分子量；性状；鉴别；游离甘油；碱性杂质、水分、炽灼残渣；脂肪酸组成；细菌内毒素（供注射用）；含量测定；类别、贮藏、标示；注等十项内容。抗坏血酸棕榈酸酯：修订名称、比旋度、鉴别、干燥失重、含量测定、贮藏共六项内容。可溶性淀粉：删去“重金属” 项和“砷盐”项；标准最后增加“注：为满足制剂稳定性和安全性要求，必要时，可对本品铅进行控制。”1、预胶化淀粉2、玉米淀粉3、豌豆淀粉4、木薯淀粉5、麦芽糊精6、马铃薯淀粉7、小麦淀粉8、果胶9、三辛酸甘油酯10、抗坏血酸棕榈酸酯11、可溶性淀粉

2023-09-21

·药明康德

下一款阿尔茨海默病重磅疗法是...

▎药明康德内容团队编辑阿尔茨海默病（AD）是痴呆症的主要类型之一，全球有数百万人受其影响。这种疾病剥夺了患者的记忆和自主能力，给他们的生活带来了沉重的打击。这也激发了全球科学家和研究者们加倍努力，不断寻找和开发新的治疗方法，旨在延缓甚至逆转这种疾病带来的不良影响。目前，有一系列药物正在进行3期临床试验，我们有理由相信，在不久的将来，其中相当一部分药物将获得批准上市，为更多的患者带来实质性的帮助。今日正值第30个“世界阿尔茨海默病日”。在这个特殊的日子里，我们不仅呼吁公众加强对阿尔茨海默病的关注和对AD患者的关爱，同时也希望提升公众对此领域治疗的认识。为此，药明康德内容团队整理了目前已获FDA批准上市或处于3期临床试验阶段的AD疗法，旨在帮助读者更深入地了解这一领域的最新疗法进展。获FDA批准上市的AD疗法有哪些？历经数十年的发展，目前共有10款AD药物获批并仍活跃在市场中。早期的AD药物研发主要针对乙酰胆碱酯酶和N-甲基-D-天冬氨酸（NMDA）受体这两个靶点。近年来，AD药物则主要集中于β淀粉样蛋白（Aβ）和Tau蛋白，这表明AD疗法研发的焦点已逐渐转向了阿尔茨海默病的病理生物标志物。其中，Leqembi（lecanemab）是近年备受关注的一款药物。它于2023年7月获得FDA的完全批准，成为了首款靶向Aβ、且由加速批准转为传统批准的阿尔茨海默病疗法。Leqembi通过与Aβ的可溶性寡聚体特异性结合发挥作用。在AD患者大脑中，Aβ水平升高会促使它们从单体聚集成为二聚体和可溶性寡聚体，最终进一步聚集成为大脑中的淀粉样蛋白沉积。以前的科学研究显示，Aβ的可溶性寡聚体表现出比单体更强的细胞毒性。Leqembi通过与它们结合，可中和并清除具有毒性的可溶性寡聚体。图片来源：123RF在一项双盲、安慰剂为对照组、平行组别的2b期临床试验中，接受Leqembi治疗的AD患者大脑中淀粉样蛋白呈现剂量与时间相关下降。接受每两周10 mg/kg剂量的Leqembi的患者自基线至第79周，大脑中淀粉样蛋白水平出现统计上的显著降低，相较之下，安慰剂组患者的淀粉样蛋白水平则维持不变。在3期临床试验中，AD患者在接受18个月的Leqembi治疗后，AD患者的CDR-SB评分（用于评估患者认知和日常功能，评分越高意味着患者临床功能越低）的增加速度降低27%，并在18个月里将淀粉样蛋白沉积水平降低约70%。这些数据表明Leqembi不仅能有效降低AD的病理生物标志物，还能显著改善患者的认知能力。鉴于这些积极进展，美国FDA在2023年1月加速批准了这一重磅疗法上市，用以治疗AD。仅仅数月后，在美国FDA召开的咨询会议中，与会专家一致认同这一疗法的有效性，以6：0的投票结果支持该疗法的完全批准。随后在7月，美国FDA宣布在确认其临床疗效后，将Leqembi由加速批准转为传统批准（traditional approval）。行业媒体Endpoints指出，Leqembi是20年来FDA首次完全批准的一款阿尔茨海默病药物。它的问世将造福大量具有未竟医疗需求的患者。图片来源：123RFAD疗法3期临床趋势如何？目前，共有17款AD药物正处于3期临床开发阶段，其中包括14款处于临床3期和3款处于临床2/3期的疗法。其中，由礼来（Eli Lilly and Company）开发的抗体疗法donanemab已完成向美国FDA递交上市申请，预计将在今年年底获得评审结果。除了donanemab，礼来旗下还有一款抗体疗法remternetug也处于3期临床开发阶段，这两款疗法的靶点均为N3pG的淀粉样蛋白亚型。通过靶向这一亚型，这些抗体药物能够特异性地与大脑中的淀粉样斑块相结合，从而促进淀粉样斑块的清除。这些药物的靶点呈现出多元化的特点，覆盖除了乙酰胆碱酯酶、淀粉样蛋白、Tau蛋白外的其他各类信号通路。这些药物涉及的病理机制也相当多元，包括蛋白错误折叠、神经保护、突触活性及神经传导和炎症等多个方向。这显示当前的研究正致力于多元化的探索，不再仅局限于传统靶点。研究人员正在尽力通过多样化的机制和路径来寻找更有效的阿尔茨海默病治疗方案。图片来源：123RF另外，目前的药物研发呈现出另一显著趋势，那就是对治疗阿尔茨海默病或其特定症状（如精神错乱和激越症状）的专注。这表明研发焦点除了专注于找到可以直接治疗阿尔茨海默病的药物外，也逐渐转向了开发能够减缓该病相关症状的药物，以期为患者提供更全面的治疗效果。在进入临床3期阶段的AD药物中，主要分为两大类：小分子药物和生物药，后者包括抗体和多肽。小分子药物占据了绝大多数，表明在当前的AD疗法研发领域，小分子药物仍然是主流选择。值得注意的是，AD诊断试剂也取得了显著进展，有些也已进入了临床3期开发阶段，这突显了除药物治疗之外，AD的诊断和监测方面的研发也得到了重视。最后，这个领域涌现了多家参与药物研发的公司，展示出该领域的研发活动旺盛和竞争激烈，预示着未来可能有更多的创新和突破。▲长按识别上方二维码，获取《阿尔茨海默病临床3期疗法盘点》列表这些疗法未来可期药物名称：KarXT研发公司：Karuna Therapeutics；再鼎医药（Zai Lab）疗法类型：小分子药物最高临床阶段：3期临床KarXT由xanomeline和trospium chloride两种有效成分构成，旨在激活大脑中的毒蕈碱型乙酰胆碱受体的同时，减少对外周毒蕈碱型乙酰胆碱受体的作用。通过刺激毒蕈碱受体M1和M4受体，受体激动剂xanomeline可缓解负面症状，如冷漠、社会驱动力减少、提高认知能力，并有助于改善其它精神症状，如幻觉和妄想。而季铵盐化合物trospium chloride为毒蕈碱受体拮抗剂，可抑制xanomeline于外周神经中的副作用。这款疗法由Karuna Therapeutics开发，再鼎公司拥有这款创新疗法在大中华区的研发权益。药物名称：AR1001研发公司：AriBio疗法类型：小分子药物最高临床阶段：3期临床AR1001是一种靶向磷酸二酯酶-5（PDE-5）的小分子抑制剂，具有治疗阿尔茨海默病的新型多药理学机制。在临床前研究中，AR1001被证明可通过抑制神经元凋亡和恢复突触可塑性而发挥神经保护作用。此外，AR1001还显示出对淀粉样斑块和tau蛋白的积极作用。AriBio已经完成了一项AR1001治疗轻至中度AD患者的2期研究。AD患者在接受治疗52周后，与基线相比，阿尔茨海默病合作试验-临床整体印象变化（ADCS-CGIC）评分分别下降了1.17分（10 mg组）和0.76分（30 mg组）。对于仅接受AR1001的轻度AD患者，10 mg组成员显示出2.4分（15.1%）的评分改善，30 mg组成员在52周时比基线改善了8.7分（46.3%，P=0.001）。在确认AR1001对轻度AD患者的治疗益处后，AriBio公司正在早期AD人群中进行3期临床研究，以检验其安全性和有效性。图片来源：123RF药物名称：AVP-786研发公司：大冢制药（Otsuka Pharmaceutical）疗法类型：小分子药物最高临床阶段：3期临床AVP-786是Avanir Pharmaceuticals旗下的一款在研第二代Nuedexta（氢溴酸右美沙芬20毫克/硫酸奎尼丁10毫克）药物，它由氘代的氢溴酸右美沙芬与硫酸奎尼丁（CYP2D6抑制剂）组成。氢溴酸右美沙芬经氘代后，可以显著降低对CYP2D6酶代谢的敏感性，从而提高生物利用度。在阿尔茨海默病患者中的3期临床试验结果显示，AVP-786可以显著改善患者的情绪状况，治疗后阿尔茨海默病患者的Cohen-Mansfield情绪激动问卷（Cohen-Mansfield Agitation Inventory，CMAI）分数得到了改善。药物名称：remternetug研发公司：礼来疗法类型：生物药最高临床阶段：3期临床Remternetug是礼来旗下一款IgG1单克隆抗体，靶向仅存在于脑淀粉样蛋白斑块中的淀粉样β肽第三个氨基酸的焦谷氨酸修饰。临床前药理学研究显示，remternetug清除PDAPP（血小板衍生生长因子驱动的人淀粉样前体蛋白）小鼠的淀粉样斑块呈剂量依赖性。当前，remternetug正在3期临床试验中进行测试。此前发布的一项1期临床试验的中期分析结果显示，remternetug可快速且稳定地减少AD受试者的淀粉样斑块。在该试验中，所有给药组中均观察到淀粉样蛋白呈剂量依赖性降低，但较小的250 mg剂量在第85天的应答程度低于较高剂量（700-2800 mg）。第169天，接受治疗的24例患者中有18例达到淀粉样蛋白清除。此外，这款药物的安全性、耐受性和药代动力学/药效学数据亦支持正在进行的3期试验。图片来源：123RF药物名称：fosgonimeton（ATH-1017）研发公司：Athira Pharma疗法类型：小分子药物最高临床阶段：2/3期临床Fosgonimeton是Athira Pharma公司开发的一款增强HGF/MET信号通路活性的小分子药物。这一通路介导健康神经系统中自然修复机制。通过靶向神经通路的修复机制，fosgonimeton具有改变疾病进程的潜力。目前，fosgonimeton在2/3期临床试验中治疗阿尔茨海默病。药物名称：benzgalantamine（ALPHA-1062）研发公司：Alpha Cognition疗法类型：小分子药物最高临床阶段：3期临床Benzgalantamine是一种已获批准的乙酰胆碱酯酶抑制剂galantamine的前药，它的分子设计可以显著降低其他乙酰胆碱酯酶抑制剂的副作用。通过向galantamine中添加苯甲酰酯，可阻断胃肠神经系统中乙酰胆碱酯酶的结合，这减少了局部神经元的过度刺激，降低了胃肠道副作用，并提高了生物利用度。Benzgalantamine一旦被吸收，就会在肝脏中代谢为活性药物和galantamine，并随着循环系统进入大脑。图片来源：药明康德内容团队制图在关键性生物等效性研究中，相较于氢溴酸加兰他敏（轻中度AD的标准治疗药物），benzgalantamine达到了生物等效的曲线下面积和峰值暴露。在这些研究中，benzgalantamine未引起任何不良反应。基于这些数据，Alpha Cognition公司计划提交benzgalantamine用于治疗轻至中度AD的新药申请（NDA）。药物名称：Valiltramiprosate（ALZ-801）研发公司：Alzheon疗法类型：小分子药物最高临床阶段：3期临床ALZ-801是Alzheon旗下一款在研口服小分子药物，为高牛磺酸（homotaurine）前体药物。ALZ-801在3期临床使用剂量下可抑制具神经毒性的淀粉样蛋白寡聚体形成，具有改变阿尔茨海默病疾病进程的潜力。ALZ-801于2017年获得美国FDA的快速通道资格。此前公布的2期临床数据显示，52周时，与基线相较，ALZ-801造成病患血浆P-tau181蛋白41%显著下降（p=0.032）。与对照组相较，神经影像学分析亦显示患者的海马区容积（Hippocampal Volume）获得保存，显示药物可能具有对脑结构的神经保护功用。此外，在第3、6个月与一年时，患者的记忆测试皆高于基线值，这与所观察到的生物标志物水平与大脑影响结果相符。在超过2000位阿尔茨海默病患者中，ALZ-801展现良好的安全性，与之前试验结果一致，没有观察到血管源性脑水肿的情形。图片来源：123RF目前这款药物仍在3期临床研究中进行测试。值得一提的是，行业媒体Endpoints指出，在此前公布的临床2期试验的1年数据中，Alzheon并没有公布患者在临床疗效上的详细数据，而这也让此药物正在进行中的临床3期试验结果显得更为重要且令人期待。药物名称：Anavex 2-73研发公司：Anavex Life Sciences疗法类型：小分子药物最高临床阶段：3期临床Anavex 2-73是一款sigma-1受体（SIGMAR1）激动剂。Sigma-1受体是细胞中的一种伴侣蛋白。已有研究显示，SIGMAR1的激活，对恢复神经细胞稳态和促进神经可塑性至关重要。目前，Anavex 2-73在多项临床试验中接受检验，探索它治疗阿尔茨海默病，帕金森病以及Rett综合征的潜力。此前公布的2b/3期试验ANAVEX2-73-AD-004试验结果显示，该药物达成主要终点与关键次要终点，可在统计上显著改善早期AD患者的认知能力。基于这些数据，Anavex表示将与监管机构协商以将Anavex 2-73带给美国、欧洲、亚太国家和地区的患者.药物名称：donanemab研发公司：礼来疗法类型：生物药最高临床阶段：3期临床Donanemab与名为N3pG的淀粉样蛋白亚型特异性结合，通过靶向这一亚型，donanemab能够特异性地与大脑中的淀粉样斑块相结合，从而促进淀粉样斑块的清除。图片来源：123RF今年7月公布的3期临床试验TRAILBLAZER-ALZ 2结果显示，donanemab可显著减缓具有阿尔茨海默病早期症状患者的认知与功能下降、延缓疾病进展。亚群分析显示，处于疾病最早阶段的受试者获益更为显著，与安慰剂相比，其认知与功能下降减缓达60%。Donanemab的上市申请已完成递交，预计将在今年年底获得审评结果。药物名称：TRx0237研发公司：TauRx Pharmaceuticals疗法类型：小分子药物最高临床阶段：3期临床TRx0237是一款靶向阿尔茨海默病tau蛋白病理的阿尔茨海默症修饰疗法。它靶向在大脑内神经细胞所形成的tau蛋白、TDP-43蛋白和突触核蛋白的异常聚集、错误折叠及其纤维缠结，而这些病理机制发生在多种不同神经退行性疾病中，包括阿尔茨海默病、额颞叶痴呆、帕金森病、路易体痴呆和进行性核上麻痹。TRx0237目前正在名为LUCIDITY的3期临床试验中进行测试，剂量为8 mg或16 mg的TRx0237将用于治疗轻度至中度疾病患者，这些患者未接受过胆碱酯酶抑制剂或memantine的治疗。此前公布的LUCIDITY试验的预先指定分析结果显示，与对照组相比，接受16 mg/天剂量的TRx0237的受试者血液中神经丝轻链在12个月内减少了93%，这与血液中的tau生物标志物（p-tau 181）显著相关。神经丝和tau蛋白对大脑中的神经元结构和功能至关重要。在AD中，tau蛋白聚集形成有毒纤维，损害神经元。这种损害的程度可以通过神经丝蛋白渗漏到血液中的数量来衡量。TRx0237对血液中神经丝轻链浓度的变化表明这款疗法对疾病病理的存在直接影响。去年4月，TRx0237的3期临床试验已经在中国获批，拟定适应症为轻度至中度AD，包括AD引起的轻度认知障碍。图片来源：123RF药物名称：masitinib研发公司：AB Science疗法类型：小分子药物最高临床阶段：3期临床Masitinib是一种口服酪氨酸激酶抑制剂，通过抑制肥大细胞和小胶质细胞/巨噬细胞活性，可能重塑神经元微环境，将神经免疫系统从神经毒性状态转换为神经保护状态，在神经退行性疾病中表现出神经保护作用。肥大细胞和小胶质细胞/巨噬细胞是存在于中枢神经系统中的一类先天性免疫细胞，越来越多的证据表明它们与神经退行性疾病如阿尔茨海默病、进行性多发性硬化和肌萎缩侧索硬化（ALS）的病理生理学有关。Masitinib一方面通过特异性抑制c-Kit、Lyn、和Fyn蛋白激酶的活性，来抑制肥大细胞的激活。另一方面，它也可通过抑制1型巨噬细胞集落刺激因子受体（MCSFR-1）来靶向小胶质细胞/巨噬细胞。在一项针对轻中度AD患者的关键性3期临床试验中，与安慰剂相较，masitinib能够显著减缓患者的认知恶化情形。根据新闻稿，这篇研究提供了首个临床证据，显示靶向先天免疫细胞是治疗可能由阿尔茨海默病引起的较晚期痴呆的有效治疗手段。药物名称：bezisterim（NE-3107）研发公司：BioVie疗法类型：小分子药物最高临床阶段：3期临床炎症是影响阿尔茨海默病、帕金森病的关键机制之一。NE-3107是BioVie公司的主要产品之一，其核心机制是通过减少炎症、提高葡萄糖利用率来保护神经元，最终改善大脑健康。具体来说，NE3107选择性地抑制炎症ERK信号通路，通过抑制炎症驱动的胰岛素抵抗和主要病理炎症级联来减少神经炎症。NE-3107目前正在开展针对阿尔茨海默病的3期试验。此前的2期临床试验结果显示，AD患者在接受NE3107治疗后认知和生物标志物水平有所改善。药物名称：琥珀八氢氨吖啶研发公司：通化金马药业疗法类型：小分子药物最高临床阶段：3期临床琥珀八氢氨吖啶是一种新的胆碱酯酶抑制剂，具有双重胆碱酯酶抑制功能，可以同时抑制乙酰胆碱酯酶和丁酰胆碱酯酶，用于治疗轻中度阿尔茨海默病。不久前，通化金马宣布琥珀八氢氨吖啶片项目召开了3期临床试验揭盲预备会，正式完成盲态数据审核。通化金马在公告中表示，该公司将进一步完成数据库锁定、揭盲及主要数据的统计分析，以及该项目上市许可申请的注册准备工作。图片来源：123RF药物名称：simufilam研发公司：Cassava Sciences疗法类型：小分子药物最高临床阶段：3期临床Simufilam是一款口服小分子化合物，它的靶点不是淀粉样蛋白，而是细丝蛋白A（filamin A，FLNA），这是在大脑中高度表达的一种支架蛋白。在AD患者大脑中，FLNA的构象发生改变，这让β淀粉样蛋白片段（Aβ42）能够通过与受体结合，引发过度磷酸化的tau蛋白的产生，以及炎性细胞因子的释放。Simufilam通过与FLNA结合，恢复其正常构象和功能，阻止Aβ42的信号传导，因此具有通过靶向一个靶点，同时减少神经变性和神经炎症的潜力。在2期临床试验中simufilam取得了积极结果，不仅表现出良好的安全性和耐受性，在探索性疗效终点方面，47%接受治疗的患者在评估认知衰退的ADAS-Cog评分上，在接受治疗1年后与基线相比，改善4.7点。Simufilam目前正在3期临床试验中进行测试，以评价其治疗轻中度阿尔茨海默病患者的效果。图片来源：123RF药物名称：tricaprilin研发公司：Cerecin疗法类型：小分子药物最高临床阶段：2/3期临床Tricaprilin是Cerecin公司开发的一款中链甘油三酯的高纯度口服制剂，它通过诱导酮症状态来改善线粒体代谢。在2a期临床研究中，在完成单剂量给药90分钟后，没有携带APOE4基因的AD患者中可观察到认知能力的改善。此外，这种认知能力的改善被证明与酮水平的增加有关。目前tricaprilin正在临床2/3期试验中进行测试。药物名称：E2814研发公司：卫材（Eisai）疗法类型：生物药最高临床阶段：2/3期临床E2814是卫材公司旗下一款抗tau蛋白的单克隆抗体。在临床前研究阶段，已观察到该抗体能有效抑制Tau蛋白在体外的聚集。同时，在模拟Tau蛋白在体内传播的实验模型中，该抗体治疗能显著减少大脑中不溶于十二烷基磺酸钠（Sarkosyl）的Tau蛋白沉积，这些发现支持了E2814用于临床开发。目前这款疗法正处于临床2/3期开发阶段。药物名称：PI-2620（18F-PI-2620）研发公司：AC Immune SA；Life Molecular Imaging疗法类型：PET显像剂最高临床阶段：3期临床18F-PI-2620是在Life Molecular Imaging和AC Immune的研究合作中发现的Tau-PET示踪剂，目前正在多项临床研究中评价其作为靶向放射性药物，用于检测人脑Tau蛋白沉积情况的潜力。4R-Tau蛋白在特定脑区的沉积是皮质基底节变性（CBD）的病理标志。Tau-PET配体18F-PI-2620对4R-Tau具有亲和力，因此该示踪剂是一种有潜力的诊断手段，可用于改善疾病诊断。目前该药物处于3期临床开发阶段。结语在今天这个特殊的纪念日，我们回顾了阿尔茨海默病研究和治疗方向的重大进展。全球的科研人员和医药公司正携手加速推进多元化的AD药物研发，不仅聚焦于病因治疗，还在症状缓解方面做出了显著努力。回顾数十年AD药物的研发历程，我们对AD未来的治疗抱持乐观态度，不论是Leqembi获得完全批准，还是正在进行中的3期临床试验的积极结果，都为我们带来了希望。除此之外，我们应该进一步加大对AD研究和治疗的关注和支持，让我们共同期待科研人员带来更多的创新和突破，为全球数百万AD患者提供更高效和全面的治疗方案，帮助他们实现更高质量的生活。同时，我们也期待社会各界能够增强对AD患者的关心和关爱，共同营造一个更加友善和包容的社会环境。大家都在看药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看）[1] Karuna Therapeutics Announces Positive Results from Phase 3 EMERGENT-3 Trial of KarXT in Schizophrenia. Retrieved Sep 19, 2023, from https://www.businesswire.com/news/home/20230320005250/en[2] AriBio Co., Ltd. Announces Topline Results from Phase 2 Study of AR1001 in Mild to Moderate Alzheimer’s Patients，Retrieved Sep 19, 2023, from https://www.businesswire.com/news/home/20211104005378/en/AriBio-Co.-Ltd.-Announces-Topline-Results-from-Phase-2-Study-of-AR1001-in-Mild-to-Moderate-Alzheimer%E2%80%99s-Patients[3] Avanir Pharmaceuticals, Inc. Reports Phase 3 Data Evaluating Investigational AVP-786 for the Treatment of Moderate-to-Severe Agitation in Patients with Alzheimer's Dementia. Retrieved Sep 19, 2023, from https://www.prnewswire.com/news-releases/avanir-pharmaceuticals-inc-reports-phase-3-data-evaluating-investigational-avp-786-for-the-treatment-of-moderate-to-severe-agitation-in-patients-with-alzheimers-dementia-300817513.html[4] Safety and Amyloid Plaque Reduction Effects of Remternetug in Patients with Alzheimer’s Disease: Interim Analysis from a Phase 1 Study. Retrieved Sep 19, 2023, from https://assets.ctfassets.net/mpejy6umgthp/51Sv0wOrFxfiHJNqcyuNYu/0c5df804e8a23256262fcb40489ae181/REMIPT3_ADPD2023_JIN_SAFETY_PLAQUE_REDUCTION_Ph1LAKB.pdf[5] ALPHA-1062，Retrieved Sep 19, 2023, from https://www.alphacognition.com/our-approach/alpha-1062/[6] Alpha Cognition Announces Positive Results from Pivotal Study with ALPHA-1062 in Development for Alzheimer’s Disease，Retrieved Sep 19, 2023, from https://www.businesswire.com/news/home/20220622005104/en/Alpha-Cognition-Announces-Positive-Results-from-Pivotal-Study-with-ALPHA-1062-in-Development-for-Alzheimer%E2%80%99s-Disease[7] Alzheon Reports Industry-Leading Biomarker, Brain Preservation and Clinical Effects Following 12 Months of Treatment in Phase 2 Trial of Oral ALZ-801 (Valiltramiprosate) in Patients with Early Alzheimer’s Disease. Retrieved Sep 19, 2023, from https://alzheon.com/alzheon-reports-industry-leading-biomarker-brain-preservation-and-clinical-effects-following-12-months-of-treatment-in-phase-2-trial-of-oral-alz-801-valiltramiprosate-in-patients-with-early-alzheim/[8] Anavex Life Sciences Announces ANAVEX®2-73 (Blarcamesine) Improved both Primary Cognitive and Secondary MDS-UPDRS Efficacy Endpoints with Significant Biomarker Correlation in Placebo-Controlled Phase 2 Clinical Trial for the Treatment of Patients with Parkinson’s Disease Dementia. Retrieved Sep 19, 2023, from https://www.anavex.com/anavex-life-sciences-announces-anavex2-73-blarcamesine-improved-both-primary-cognitive-and-secondary-mds-updrs-efficacy-endpoints-with-significant-biomarker-correlation-in-placebo-controlled-p/[9] TauRx’s hydromethylthionine mesylate (HMTM) demonstrates significant reduction in neurodegeneration in Alzheimer’s Disease (AD)，Retrieved Sep 19, 2023, from https://taurx.com/news-insights/taurxs-hydromethylthionine-mesylate-hmtm-demonstrates-significant-reduction-in-neurodegeneration-in-alzheimers-disease-ad[10] AB Science today announced publication of results from its positive pivotal phase 3 trial of masitinib in mild-to-moderate Alzheimer’s disease (AD) in Alzheimer’s Research & Therapy. Retrieved Sep 19, 2023, from https://www.ab-science.com/publication-of-the-masitinib-pivotal-phase-3-clinical-trial-in-alzheimers-disease-in-the-journal-alzheimers-research-therapy/[11] Alzheimer’s Innovations，Retrieved Sep 19, 2023, from https://bioviepharma.com/innovations/alzheimers/[12] Cassava Sciences Announces Positive Top-Line Clinical Results in Phase 2 Study Evaluating Simufilam in Alzheimer’s Disease. Retrieved Sep 19, 2023, from https://www.globenewswire.com/news-release/2023/01/24/2594355/8339/en/Cassava-Sciences-Announces-Positive-Top-Line-Clinical-Results-in-Phase-2-Study-Evaluating-Simufilam-in-Alzheimer-s-Disease.html[13] Reger et al. Neurobiology of Aging ; 2004; 25:311[14] Tricaprilin，Retrieved Sep 19, 2023, from https://www.cerecin.com/tricaprilin.html[15] AC Immune Partner LMI Progresses Tau PET Tracer PI-2620 Into Late-Stage Development In Alzheimer’s Disease，Retrieved Sep 19, 2023, from https://ir.acimmune.com/news-releases/news-release-details/ac-immune-partner-lmi-progresses-tau-pet-tracer-pi-2620-late免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床3期加速审批上市批准临床结果临床2期

2023-09-19

·BioSpace

Cerecin strengthens position in neurometabolism with addition to pipeline

Cerecin completes in-licensing of an investigational radiolabelled tracer 18FBHB, CER-022, for development and use in positron emission tomography (PET) studies of ketone body metabolism Company expands ketogenic platform following pilot data of CER-0001 in migraine and infantile spasms. CER-022 is a novel diagnostic asset with potential applications in neurology and other therapeutic indications DENVER, Colo. and SINGAPORE, Sept. 19, 2023 /PRNewswire/ -- Cerecin Inc., a clinical-stage biotechnology company pioneering innovative neurotherapeutics, today announced the in-license of CER-022 from the University of Alberta. The in-license is part of Cerecin's pipeline expansion and further strengthens its position as a leader in neurometabolism, addressing metabolic targets and bioenergetics in disease. CER-022 could have broad applications in the study of ketone body metabolism and will complement Cerecin's ongoing studies of ketosis in migraine, Alzheimer's disease and infantile spasms epilepsy. CER-022 is an 18Fluorinated beta-hydroxybutyrate ([18F]FBHB) for investigational use in positron emission tomography (PET) studies of ketone body metabolism. PET is an imaging technique using radiolabelled isotopes to measure metabolic activity in cells. CER-022 was developed by Dr. Frank Wuest, Professor of Oncology at the University of Alberta, and colleagues. This month, the U.S. Patent and Trademark Office (USPTO) issued a Notice of Allowance for the U.S. Patent Application No. 16/992,940, title: Fluorinated beta-hydroxybutyric acids for PET imaging, licensed to Cerecin by the University of Alberta. 18F radiolabeled 2-deoxyglucose (18FDG) is used in numerous applications relating to the brain, heart and in cancer diagnosis. 18FDG PET has been a transformative diagnostic enabling a better understating of tissue metabolism and the early detection and treatment of diseases, particularly cancers and cardiac function. Similarly, it is hoped that CER-022 will be an important diagnostic tool with broad applications, being of significant value to the Company in future studies of its lead investigational drug compound, CER-0001 (tricaprilin). Commenting on the in-license, Dr Samuel Henderson, Chief Scientific Officer, Cerecin, said, "We are pleased to have in-licensed this technology from the University of Alberta. Radiolabeled glucose has proven to be a valuable tool for the study of many diseases, and with the growing interest in ketone body metabolism, a tool to study ketosis may have similar broad uses. Studies using CER-022 may increase our knowledge of the role of ketosis in a variety of applications." Dr. Frank Wuest, Professor at the University of Alberta said, "Our partnership with Cerecin will advance the study of our molecular imaging technologies and evaluate if CER-022 will be a useful tool for studying ketone body metabolism using PET. Disorders exhibiting altered energy substrate utilization, such as Alzheimer's disease, epilepsy, diabetes, and cancer may be of interest for PET imaging studies using CER-022." About Cerecin Cerecin is a clinical-stage biotechnology company focused on developing drugs that target the metabolic bases of central nervous system diseases. Cerecin's lead compound, CER-0001, is being developed for migraine, Alzheimer's disease and epilepsy. Cerecin's programs leverage its extensive experience in neurology and global drug development. Cerecin is supported by two multinational partners, Nestlé S.A. (NSRGY), and Wilmar International Limited (F34.SI), as well as a syndicate of leading institutional investors. By bringing together the deep expertise of its leadership team and highly innovative programs, Cerecin is becoming a global leader in bioenergetics and neurometabolism. Forward looking statements This press release contains "forward-looking statements" under applicable securities laws that are based on the current expectations and beliefs of Cerecin. Such statements may be accompanied by words such as "aim," "anticipate," "believe," "could," "estimate," "expect," "forecast," "intend," "may," "plan," "potential," "possible," "will" and other words and terms of similar meaning. All statements, except for statements of historical fact, are statements that could be deemed forward-looking statements, including but not limited to: (i) sources and availability of third party financing and investments and the projected financial performance of the Company; (ii) the expected development of the Company's business, projects, drug development programs and joint ventures; (iii) execution of the Company's vision and growth strategy, including with respect to future growth; and (iv) new developments with respect to the Company's projects that are currently underway, in development or otherwise under consideration. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. Forward-looking statements are not guaranties of future performance and undue reliance should not be placed on them. Such forward-looking statements necessarily involve known and unknown risks and uncertainties, which may cause actual performance and financial results in future periods to differ materially from projections of future performance or any result that may be expressed or implied by such forward-looking statements. Although forward-looking statements contained in this press release are based upon what management of Cerecin believes are reasonable assumptions, there can be no assurance or guarantee that forward-looking statements will prove to be accurate, as actual results and future events could differ materially from those anticipated in such statements. Cerecin undertakes no obligation to update forward-looking statements if circumstances or management's estimates or opinions should change except as required by applicable securities laws. The reader is cautioned not to place undue reliance on forward-looking statements. For more information visit . For further information, please contact: pr@cerecin.com © 2023 Cerecin AC-23-973 View original content to download multimedia: SOURCE Cerecin

引进/卖出

100 项与三辛酸甘油酯相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	三辛酸甘油酯	N07	DB12176

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
阿尔茨海默症	美国	-	1993-01-01

未上市

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适应症	最高研发状态	国家/地区	公司	日期
帕金森病	临床2期	美国	Cerecin, Inc.	2022-07-15
偏头痛	临床2期	澳大利亚	Cerecin, Inc.	2020-12-17
记忆障碍	临床2期	美国	Cerecin, Inc.	2006-07-01
癫痫	临床1期	美国	Cerecin, Inc.	2022-07-15
婴儿痉挛	临床1期	澳大利亚	Cerecin, Inc.	2021-11-01
婴儿痉挛	临床1期	新加坡	Cerecin, Inc.	2021-11-01
味觉障碍	临床1期	美国	Cerecin, Inc.	2018-09-10

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分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04437199 (Corporate Publications) 人工标引	临床2期	偏头痛	81	Tricaprylin	蓋壓構繭夢衊鑰淵蓋窪(壓蓋願鏇齋鏇夢遞願遞) = For Part 1, there was no meaningful difference in the primary endpoint between treatment arms during Month 3. 廠醖選鹹蓋鏇製衊淵願 (積鏇遞繭簾衊築製餘鑰 )	积极	2022-11-25
				Placebo
NCT01741194 (NOURISH AD, Pubmed \| J Alzheimers Dis) 人工标引	临床2/3期	阿尔茨海默症	413	AC-1204	鹹廠網鬱鹽夢憲醖遞簾(鏇範觸鹹製餘遞廠顧淵) = 壓壓淵齋製齋齋築構築簾夢顧獵廠膚獵鬱醖繭 (鑰壓鹽繭築積艱繭積顧 )	不佳	2020-01-01
				Placebo	鹹廠網鬱鹽夢憲醖遞簾(鏇範觸鹹製餘遞廠顧淵) = 構夢獵願艱衊選製襯鹹簾夢顧獵廠膚獵鬱醖繭 (鑰壓鹽繭築積艱繭積顧 )
NCT00142805 (Pubmed \| Nutr Metab (Lond))	临床2期	阿尔茨海默症	152	AC-1202	鏇鹽衊餘蓋壓簾範憲積(範蓋襯廠簾選淵鏇鑰積) = 獵艱鏇積齋獵築憲糧願繭獵鑰糧艱蓋構網鬱鑰 (觸窪鏇網簾構繭膚鏇壓 )	积极	2009-08-10