Core Viewpoint - The National Health Commission of China has prohibited the use of "cervical deep lymphatic vessel/lymph node-venous anastomosis" for the treatment of Alzheimer's disease due to insufficient clinical evidence supporting its safety and efficacy [1][4]. Group 1: Regulatory Actions - The National Health Commission organized an expert evaluation of the technique, concluding that it is still in the early exploratory stage of clinical research, with unclear indications and contraindications [1][4]. - Local health authorities are required to ensure that medical institutions cease the use of this technique for Alzheimer's treatment and provide follow-up services for affected patients [1][5]. - Institutions and personnel continuing to use this technique post-notification will face serious consequences under relevant health laws and regulations [2]. Group 2: Technical Overview - "Cervical deep lymphatic vessel/lymph node-venous anastomosis" is a microsurgical technique that connects lymphatic vessels or nodes to nearby veins, primarily used for treating persistent lymphedema [3]. Group 3: Evaluation Findings - The evaluation found a lack of direct evidence from preclinical studies regarding the safety, efficacy, and economic viability of the technique for Alzheimer's treatment [4]. - The technique's application for Alzheimer's disease lacks high-quality evidence from clinical studies and health economics [4]. Group 4: Implementation Guidelines - Provincial health authorities must fulfill their responsibilities in managing the clinical application of medical technologies and enhance daily supervision of medical institutions [5]. - Local health departments should conduct investigations into the clinical application of the technique and ensure compliance with the prohibition [5].

Core Viewpoint - The National Health Commission has issued two important notifications prohibiting specific surgical techniques for the treatment of Alzheimer's disease and type 2 diabetes, emphasizing the need for clinical application management and evidence-based support for medical practices [1]. Group 1: Alzheimer's Disease Treatment - The notification prohibits the use of "cervical deep lymphatic vessel/lymph node-venous anastomosis" for treating Alzheimer's disease due to its early exploratory stage in clinical research [1]. - Expert evaluations indicate that the indications and contraindications for this technique are not clearly defined, and there is a lack of high-quality evidence supporting its safety and effectiveness [1]. Group 2: Type 2 Diabetes Treatment - The notification also bans the use of "jejunum-ileum anastomosis" for the treatment of type 2 diabetes, reflecting similar concerns regarding the clinical application of this surgical method [1]. - The decision underscores the importance of rigorous evaluation and evidence before adopting new medical technologies in clinical settings [1].

国家卫生健康委办公厅日前发布关于禁止将"颈深淋巴管/结—静脉吻合术"应用于阿尔茨海默病治疗的 通知。通知提出，国家卫生健康委近期获悉有个别医疗机构开展"颈深淋巴管/结—静脉吻合术"治疗阿 尔茨海默病，为进一步加强医疗技术临床应用管理，国家卫生健康委组织专家对该技术进行评估，评估 认为该技术处于临床研究早期探索阶段，适应证及禁忌证尚不明确，安全性、有效性缺乏高质量循证医 学证据支撑。根据《医疗技术临床应用管理办法》(国家卫生健康委员会令第1号)有关规定，决定禁止 将"颈深淋巴管/结—静脉吻合术"应用于阿尔茨海默病治疗。 ...

Core Viewpoint - Tencent's cognitive training software "Tencent Brain Exercise" has received medical device registration approval from the Guangdong Provincial Drug Administration, marking its entry into clinical application for improving cognitive abilities in patients with mild cognitive impairment (MCI) [1][3] Industry Overview - The cognitive digital therapy market in China has over 40 companies focusing on this area, with 47 cognitive digital therapy software products approved by the National Medical Products Administration as of October 2024 [2] - The market for cognitive impairment digital therapy is expected to grow significantly, with a projected market size of 2.686 billion yuan in 2023, increasing to 10.467 billion yuan by 2025 and 89.274 billion yuan by 2030, reflecting compound annual growth rates of 97.4% and 53.5% respectively [4] - The number of MCI patients in China is approximately 38.77 million, with a prevalence rate of 15.5%, indicating a substantial patient base driving demand for cognitive digital therapies [4] Company Insights - Tencent's "Tencent Brain Exercise" transforms traditional cognitive rehabilitation into a mobile application format, utilizing gamified cognitive training based on evidence-based medicine principles [3] - The company aims to address the challenges of commercializing digital therapies, as the current business models are still in the early stages of development [1][2] - Brain Dynamics, a competitor in the market, has achieved a market share of 25.0% in the cognitive digital therapy market and 91.6% in the medical-grade cognitive digital therapy market in China, but faces challenges in profitability despite significant revenue growth [5] Challenges in the Market - The cognitive digital therapy sector is experiencing high market education costs and is still in the exploratory phase regarding application scenarios [1][2] - Regulatory challenges exist, as clinical experts have varying opinions on the clinical use of digital therapy products, which complicates their appropriate application [4][5] - The industry faces difficulties in ensuring that payers (such as insurance companies and hospitals) are willing to cover these therapies, which is crucial for sustainable business models [1][2] Competitive Landscape - Major tech companies like Tencent, Alibaba, and ByteDance are entering the healthcare sector, but a mature commercialization model is still needed [6] - The cognitive digital therapy market is characterized by a mix of substantial patient demand and ongoing challenges in commercialization pathways, creating a complex development landscape [2][4]

撰文丨王聪 编辑丨王多鱼 排版丨水成文 晚发性阿尔茨海默病 （Late-Onset Alzheimer's Disease, LOAD） 是指 65 岁之后发病的阿尔茨海默病 （AD） ，占所有阿尔茨海默病的 90% 以上。全基因组关联研究 （GWAS） 已确定了多个 与 LOAD 发病 风险增加相关的基因多态性，许多与 LOAD 风险相关的等位基因通过影响 小胶质细胞 （microglia，MG） 的先天免疫反应和脂质代谢来改变疾病的发生机制。 2025 年 6 月 9 日，西达赛奈医疗中心的研究人员在 Nature 子刊 Nature Aging 上发表了题为： Boosting angiotensin-converting enzyme (ACE) in microglia protects against Alzheimer's disease in 5xFAD mice 的研究论文。 该研究显示，在小胶质细胞中增强 ACE 表达，能够保护阿尔茨海默病小鼠模型的大脑，表明了 表达 ACE 的小胶质细胞可能作为一种治疗阿尔茨海默病的新型细胞疗法。 血管紧张素转换酶 （ACE） 是一种在 全基因组关联研究 ...

Core Viewpoint - The production of Manzoutan capsules, used for treating Alzheimer's disease, has been halted due to the expiration of its drug registration certificate, with the company awaiting approval from the drug regulatory authority [1][8]. Company Summary - Green Valley Pharmaceutical Technology has confirmed the closure of its office and production areas related to Manzoutan capsules, citing the expiration of the drug registration certificate and the ongoing wait for regulatory approval [1][8]. - The company previously acknowledged the difficulties patients faced in obtaining the medication and expressed regret over the potential impact of drug interruptions on patients' conditions [8]. Market Summary - The market price of Manzoutan capsules has surged approximately 40% in recent months, with prices on e-commerce platforms ranging from 428 yuan to 534.5 yuan per box, and some pharmacies listing prices as high as 5000 yuan per box [4]. - Reports indicate that many patients are struggling to find the medication, with numerous complaints about stock shortages and price hikes on social media [5][4]. Regulatory Summary - The approval status of Manzoutan capsules is currently pending, having entered the review queue on October 25, 2024. The situation of halting production due to expired licenses is considered rare in the industry [8][9]. - Manzoutan capsules were conditionally approved for market entry in China in November 2019, marking it as the first new drug for Alzheimer's disease approved globally since 2003 [8][9]. Clinical Summary - Concerns regarding the efficacy and safety of Manzoutan capsules persist, as the drug was approved under conditions requiring further research on its pharmacological mechanisms and long-term safety [9]. - The three-phase clinical trial for Manzoutan lasted only 36 weeks, which is deemed insufficient for a chronic degenerative disease like Alzheimer's, typically requiring longer observation periods to confirm sustained cognitive improvement [9].

Core Viewpoint - The company, Green Valley Pharmaceutical Technology, has announced the suspension of production for the mannitol sodium capsule product line due to the expiration of its drug registration certificate, currently awaiting approval from the drug regulatory authority [1] Group 1: Company Actions and Responses - Green Valley Pharmaceutical Technology has halted the production of mannitol sodium capsules and will close related office and production areas [1] - Employees affected by the suspension will receive wages at the minimum wage standard set by Shanghai, with social security and housing funds being paid normally [1] - The company has committed to restoring original salary standards once its operational conditions improve and it regains the ability to pay [1] Group 2: Product Background and Market Impact - Mannitol sodium capsules, developed in collaboration with Ocean University of China and the Shanghai Institute of Materia Medica, are used for mild to moderate Alzheimer's disease to improve cognitive function [1] - Since its launch in November 2019, the drug has benefited over 500,000 patients, with projected sales exceeding 2.1 million boxes in 2024 [1] - There is currently a shortage of mannitol sodium across the country, with prices on online platforms fluctuating daily [1] - The company has received over 9,300 requests from Alzheimer's patients for purchasing the drug through its hotline and online platforms [1] Group 3: Clinical Research and Development - The mechanism of action of mannitol sodium was published in a cover article in "Cell Research" in 2019, and further validation studies were published in 2024 [2] - An international Phase III clinical trial was initiated in 2020 but was abruptly halted in May 2022 due to increased dropout rates and funding issues [2] - Domestic post-marketing clinical research has involved 3,300 patients, with mid-term analysis showing 16% of patients exhibiting stable or improved efficacy indicators [3] - The final results of the post-marketing study are expected to be presented at an international academic conference in the second half of 2025 [3] Group 4: Industry Context - Alzheimer's disease remains a significant challenge in the medical field, with few new drugs approved since 2003, primarily focusing on symptom improvement [3] - Major pharmaceutical companies, including Eli Lilly, Takeda, Merck, Pfizer, and Roche, have entered the market, but no groundbreaking drugs have emerged yet [3] - The strategy for treating Alzheimer's is diversifying, with a growing number of clinical trials focusing on neuroinflammation rather than solely relying on amyloid-beta [3]

Core Viewpoint - The company, Green Valley Pharmaceutical Technology, has halted the production of its controversial drug, Glycyrrhizin Sodium Capsules, which is intended for the treatment of mild to moderate Alzheimer's disease, due to severe operational pressures and cash flow issues [2][4][6]. Group 1: Product and Regulatory Status - Glycyrrhizin Sodium Capsules received conditional approval from the National Medical Products Administration in November 2019, with requirements for further studies on carcinogenicity and pharmacological mechanisms [2]. - The drug's international Phase III clinical trial, which aimed to recruit 2,046 participants across China, the U.S., and Europe, was stopped in May 2022 due to factors such as the pandemic and funding issues [2][4]. - The company announced on May 30, 2025, that it would cease operations related to the Glycyrrhizin Sodium product line, pending the approval of its drug registration certificate [2][3]. Group 2: Industry Context and Challenges - Alzheimer's disease presents a significant challenge for the medical community, with global pharmaceutical companies investing hundreds of billions of dollars in research, yet most have failed to produce effective treatments [4]. - The company previously conducted post-marketing clinical research on Glycyrrhizin Sodium, involving 3,300 patients across China, with results expected to be presented at an international academic conference in the second half of 2025 [5]. - The ongoing operational difficulties and cash flow constraints have left the future of this controversial drug uncertain [6].

Core Points - The company, Green Valley Pharmaceutical Technology, is facing severe operational difficulties and extreme cash flow constraints [4][5] - The product, Gannuo Sodium Capsules, has reached a critical turning point in its product lifecycle, leading to the suspension of its production and related operations [2][5] - The drug, which is intended for the treatment of mild to moderate Alzheimer's disease, has been controversial due to questions surrounding its efficacy and clinical trial processes [2][4] Company Summary - Green Valley has halted the production of Gannuo Sodium Capsules and is closing relevant office and production areas [2] - The drug received conditional approval from the National Medical Products Administration in November 2019, with specific requirements for further studies and safety evaluations [2] - The company announced the suspension of international Phase III clinical trials in May 2022, citing factors such as the pandemic and funding issues [2] Industry Context - Alzheimer's disease presents a significant challenge for the medical community, with a complex pathogenesis and a long disease course, impacting many patients globally, particularly in an aging Chinese society [4] - Major pharmaceutical companies have invested hundreds of billions of dollars in the development of Alzheimer's treatments, with very few new drugs approved in the last two decades, primarily focusing on symptom management [4]

Core Viewpoint - Alzheimer's disease (AD) is a destructive neurodegenerative disorder characterized by gradual cognitive decline, necessitating therapies that can slow or halt its progression [2][6]. Group 1: Current Treatments and Limitations - Currently, only a few FDA-approved monoclonal antibodies targeting amyloid-beta (Aβ) are available for early-stage Alzheimer's treatment, such as Lecanemab and Donanemab, which show efficacy in reducing amyloid burden but have limited impact on disease progression [2]. - The focus on Aβ alone is insufficient to address the progressive nature of Alzheimer's disease [2]. Group 2: Gene Therapy as a Promising Strategy - Gene therapy that enhances intrinsic neuroprotective pathways presents a promising new strategy to slow neurodegenerative changes and prevent further cognitive decline [3][6]. - Caveolin-1 (Cav-1), a membrane scaffolding protein, regulates various growth-promoting and survival signaling pathways, indicating its potential in Alzheimer's treatment [6]. Group 3: Research Findings - A recent study from the University of California, San Diego, demonstrated that delivering Cav-1 via AAV9 to symptomatic Alzheimer's mouse models can mitigate cognitive loss and pathological transcriptome changes [4][5]. - The study involved administering SynCav1 to symptomatic Alzheimer's mouse models (PSAPP and APPKI) and showed that it maintained hippocampal-dependent memory abilities [7][8]. - Transcriptomic analysis indicated that the profiles of PSAPP-SynCav1 mice were similar to those of age-matched wild-type mice, with downregulation of neurodegenerative pathways and upregulation of synaptic and cognitive-related pathways [8][10]. Group 4: Mechanisms of Action - The delivery of SynCav1 to the hippocampus during the symptomatic stage protected learning and memory abilities, with increased expression levels of p-CaMKII and p-CREB in primary cortical neurons, suggesting enhanced neuronal and synaptic activity [10]. - Activity-dependent neuroprotective protein (ADNP) was identified as a potential mediator of SynCav1's neuroprotective effects, retaining PAC1R, a known regulator of ADNP expression [11][12].