Core Viewpoint - The article discusses the significant breakthrough in spinal cord injury (SCI) treatment through the discovery of Thiorphan, a drug that promotes neuronal regeneration and functional recovery after SCI, offering new hope for patients suffering from paralysis and disability [2][3][6]. Group 1: Research Findings - A study published in Nature identified Thiorphan as a candidate drug that reprograms neurons to enhance recovery after spinal cord injury [3]. - Thiorphan, originally developed as a neutral endopeptidase inhibitor for treating diarrhea, has shown remarkable potential in promoting nerve regeneration and functional recovery in SCI models [11][19]. - In experiments with adult mice, Thiorphan increased total neurite growth by 80% and the longest neurite length by 30%, demonstrating a dose-dependent effect [12]. Group 2: Experimental Validation - In a rat model of severe cervical spinal cord injury, treatment with Thiorphan initiated two weeks post-injury resulted in a twofold increase in forelimb grasp success rate, improving accuracy from 30% to 60% when combined with neural stem cell transplantation [14]. - Anatomical evidence indicated that Thiorphan treatment led to a 60% increase in the regeneration of corticospinal axons, establishing synaptic connections across the injury site [15]. - Thiorphan was also effective in promoting growth in cortical neurons from both adult macaques and a 56-year-old human, with increases of 30.3% in total neurite growth and 23% in the longest neurite length [16]. Group 3: Mechanism of Action - The mechanism of Thiorphan involves upregulating brain-derived neurotrophic factor (BDNF) and phosphorylated AKT, allowing neurons to revert to a developmental state and regain growth capabilities [17]. - Given that Thiorphan has been safely used in humans, the clinical development risk is significantly reduced [19]. Group 4: Future Directions - The research team is exploring more convenient administration methods, including intrathecal injection or systemic delivery, and developing derivatives with better blood-brain barrier permeability [20]. - This study not only identifies a promising candidate for SCI treatment but also establishes a new paradigm for drug development from computer screening to human validation, which could be applied to other neurological and neurodegenerative diseases [20].

该研究以： AI-enabled drug prediction and gene network analysis reveal therapeutic use of vorinostat for Rett Syndrome in preclinical models 为题，于 2025 年 7 月 1 日，发表在了 Communications Medicine 期刊。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 开发出一种有效的 Rett 综合征 疗法一直极具挑战性，这在很大程度上是因为这种罕见的遗传疾病 （ 每 10000 名女孩中就有 1 名患病 ） 所伴有的认知和身体 损伤十分复杂，患者因 X 染色体上的 MeCP2 基因突变，导致出现重复的手部动作、语言障碍和癫痫发作，同时还伴有非神经系统器官 （ 包括消化系统、肌肉 骨骼系统和免疫系统 ） 的问题。 而现在，哈佛大学 Wyss 研究所的研究团队通过利用人工智能 （AI） 驱动的药物发现流程取得了重大突破，他们发现，一种名为 伏立诺他 （ Vorinostat， 一种 已获美国 FDA 批准用于治疗皮肤 T 细胞淋巴瘤的组蛋白去乙酰化酶抑制剂） 的药 ...

Core Viewpoint - The innovative drug sector in the A-share market has seen significant stock price increases, with several leading companies achieving over 100% growth in 2023, driven by breakthroughs in new drug development [1] Group 1: Company Developments - Shuyou Shen's investigational drug for hemophilia has received breakthrough therapy designation and has submitted a conditional marketing application [1] - Taiankang's innovative drug CKBA ointment has been recognized for its research published in the top immunology journal, Immunity, highlighting its potential in treating vitiligo [1][2] - The research team led by Wang Honglin at Shanghai Jiao Tong University has identified a novel pathogenic mechanism in vitiligo involving sensory neurons and CGRP, which could lead to new treatment strategies [6][7] Group 2: Clinical Trials and Research Findings - The study revealed that blocking the CGRP receptor with Rimegepant significantly inhibits disease progression in vitiligo mouse models and shows promising results in a clinical trial with 57 patients [2][8] - The ongoing Phase II clinical trial for CKBA ointment aims to evaluate its safety and efficacy in non-segmental vitiligo patients, with results expected in July 2023 [11] - The research indicates that CKBA ointment can effectively suppress autoreactive CD8+ T cells, offering a differentiated approach compared to existing treatments [12] Group 3: Market Potential - The global prevalence of vitiligo is estimated at 0.5% to 2%, with approximately 30 million patients in China, indicating a substantial market opportunity for effective treatments [9][12] - The potential market for innovative vitiligo drugs in China is projected to exceed 20 billion yuan, highlighting the demand for targeted therapies [12] - Despite the approval of Ruxolitinib for vitiligo, its market share remains limited, underscoring the need for new therapies to meet patient needs [12]