NEUROD1

SUZHOU, China, March 21, 2024 /PRNewswire/ -- NeuExcell Therapeutics, a leading biotechnology company focused on in vivo neural regenerative therapies, announces the successful dosing of the first patient with the first-in-class NeuroD1 gene therapy product NXL-004. This milestone represents significant progress in the development of new treatment for malignant glioma patients. Led by Professor Yulun Huang and his team at the Fourth Affiliated Hospital of Soochow University in Suzhou, China, the investigator-initiated trial (IIT) will evaluate the safety and tolerability of NeuExcell's AAV-NeuroD1 gene therapy product NXL-004 in patients with glioblastoma. This clinical study marks the first clinical use of AAV-NeuroD1 gene therapy to treat patients worldwide. Glioblastoma is a highly aggressive form of brain cancer with limited treatment options and poor prognosis. NXL-004, based on NeuExcell's revolutionary in vivo trans-differentiation technology platform, aims to inhibit tumor cell proliferation and promote their transformation into neural cells through the overexpression of the NeuroD1 transcription factor. The advantage of this glioma cell trans-differentiation approach is minimal side-effect on other brain cells, which is distinct from radiation or chemotherapy that has collateral damage on healthy cells. Promising preclinical results from animal model studies have paved the way for this groundbreaking clinical trial, offering hope for many patients suffering from debilitating brain disorders such as malignant glioma. "We are very excited about completing the dosing of the first patient using NeuroD1 gene therapy product NXL-004 in this exploratory clinical study," said Dr. Yulun Huang, the study's lead investigator. "This milestone underscores the dedication of our team to try innovative approaches in addressing unmet medical needs such as glioblastoma. We are committed to closely monitor the patient and evaluate the safety and efficacy of NXL-004 in this trial." Professor Gong Chen, the inventor of in vivo neural regenerative gene therapy and the founder of NeuExcell Therapeutics, expressed his gratitude: "We are grateful to Professor Yulun Huang and his team for their outstanding work. This first-in-human trial sets an important milestone for our first-in-class NeuroD1 gene therapy that has the potential to treat millions of patients suffering from severe neurological disorders. We are dedicated to developing game-changing treatments for neurodegenerative diseases using in vivo neural regenerative therapies." About NeuExcell Therapeutics: NeuExcell Therapeutics is a leading biotechnology company focused on developing innovative neural regenerative therapies to address unmet medical needs in the field of neurodegenerative diseases and cancers. NeuExcell is committed to revolutionizing the field of CNS drug development and improving outcomes for patients worldwide.

“健康衰老”正逐步发展成为新的消费市场。发展面向人民生命健康的生物医药产业，满足人民群众对生命健康更高要求，推动大健康产业的快速发展，吸引着越来越多制药企业、地方政府、产业园区的关注。2024年1月6日，由中共江阴市委、江阴市人民政府主办，江阴国家高新区承办，同写意策划的“健康未来论坛”顺利举办。本次论坛以“科学抗衰，永无止境”为主题。聚焦生命健康战略前沿和时代风口、通过对话顶级专家、拓展生物技术投资商业化路径，帮助Biotech穿越资本寒冬，打造全新创新生态、共享生物技术发展机遇。领导致辞曲凤宏第十三届全国政协副秘书长中国药学会副理事长抗衰老、追求健康寿命是人类的永恒主题。在消费升级、健康需求深化的情况下，全球延缓衰老的需求日益增长，抗衰老行业持续扩容。干细胞抗衰老行业作为一项的新兴产业，在全球表现出相当强大的市场前景和庞大的利润空间。我国正采取一系列措施减缓老龄化社会趋势，在干细胞及再生医学领域从政策等多方面给予大力支持，为干细胞抗衰老行业的蓬勃发展创造了有利的环境。主旨报告张自然医药行业研究专家掘金中国非医保市场：潜力与机遇干细胞尚未纳入医保，暂只能深耕非医保市场。非医保市场潜力也很大，如片仔癀、安宫牛黄丸、云南白药牙膏等非医保产品在院外市场也都取得了耀眼的成绩。全国居民人均医疗保健支出在消费性总支出的占比越来越高，去年前三个季度已达9.4%。目前，我国还有相当数量非医保定点的零售药店和医疗机构，这都为非医保产品提供了巨大的市场空间。吴朝晖中国医药生物技术协会驻会副理事长干细胞与健康产业：未来发展与监管趋势随着人口老龄化导致老年性疾病增长，人们对生活质量的追求，干细胞抗衰老和医美的市场需求逐渐增多。但现实问题是缺乏系统性的干细胞抗衰老、医美基础研究，也缺乏高水平的循证医学证据，其应用也未有规范，同时还面临着细胞安全、政策，以及法律层面的风险。目前，干细胞在健康领域的应用，干细胞治疗按照药品进行管理是主渠道，但对干细胞健康消费的监管仍需要积极探索和进一步规范。王小宁教授，国家老年疾病临床中心副主任抗衰老产业新支撑，老龄科学（Geroscience）展望Geroscience旨在通过多维度探讨增龄驱动的慢病机制，通过抗衰老，延缓慢病发生，改善慢病指标，延长健康寿命。老龄科学更关注生物年龄，增龄科学则强调增加年龄对全生命周期的影响。慢性疾病或衰老过程中的核心是“僵尸细胞”，其残骸也是干预衰老评估的一个切入点。肌肉、味觉替代和家政机器人是提高生活质量的产业关注点，其中，肌肉的作用远远被低估。赵春华中国医学科学院北京协和医学院主任973首席欧洲科学、艺术与人文学院院士干细胞医疗干预组织衰老治未病研究亚全能干细胞（PEPSC）的提出首次从根本上解决了细胞医药工程的种子细胞来源问题，其保留了全能干细胞基因表型、表观遗传学表型，小RNA表达谱分化关键分子组蛋白活化状态等水平上阐明了多胚层分化能力，但成体干细胞转分化效率低而成为其临床转化的瓶颈。多潜能干细胞（PEPSCs）是多胚层来源、具有自我更新和多向分化潜能的多能干细胞，兼有重要免疫双向调控作用，是临床上细胞疗法的理想细胞来源。未来，细胞医药还可通过中西医结合的方式，推动我国健康医学发展。姬广聚中国科学院生物物理研究所研究员俄罗斯自然科学院外籍院士基于RNA技术的抗衰老与逆龄研究衰老的本质是细胞的衰老，而细胞衰老指“细胞周期的永久性阻滞”。如果能够逆转细胞衰老，使衰老细胞重回细胞周期，也就意味着“逆龄”。我们团队的研究证明，通过核酸技术，衰老可以被逆转：小鼠实验中，对照组和治疗组分别给予不同样品，治疗后，实验鼠在体貌状态和生存时长、活动、抓力和体重、生物标志物检测等各项活动和生理指标上，都向更年轻的状态发生了逆转，使老年鼠学习、记忆、空间辨识能力等认知功能恢复到年轻状态。陈功神曦生物创始人兼首席科学家神经再生基因疗法逆转大脑衰老脑细胞由神经元和胶质细胞组成，神经元不能分裂，但胶质细胞可以自我分裂再生。实验证明，原位转分化改善AD小鼠的记忆功能，NeuroD1显著修复大鼠海马损伤，MRI显示NeuroD1显著抑制海马萎缩，促进海马区神经元活动恢复，灵长类猴脑内更是再生千万级神经元。相信原位神经再生技术将是解决神经科性疾病，包括大脑逆转衰老的一把金钥匙。周国瑛亦诺微医药创始人、董事长兼CEO基于外泌体技术，开发医美产品亦诺微管线中的H633是在研的抗脱发、助生发产品。实验显示，H633显著增加毛囊数量和毛囊长度，促进毛囊正常化，使新生毛发长长、长密，同时显著提高毛囊生长期/休止期比值，使毛囊正常进入生长期，维持毛发持久健康生长，产品正在进行人体功效研究。H611可抗多种皱纹，实验中可显著刺激皮肤成纤维细胞的增殖活性，促进皮肤成纤维细胞表达“水分传输带”水通道蛋白AQP3，肌肤保水，已经完成全部开发包括人体功效。同时，祛斑产品H612 也完成开发，有了人体数据。此外，最新研发的白发转黑发产品H635正在进行人体功效研究。吕宇轩德国马普衰老研究所研究员导向安全、有效和实用的衰老保护老龄化是老年相关疾病（ARDs）的最大风险因素。以雷帕霉素为例，可通过持续增强肠道自噬功能，在成年早期从短暂的雷帕霉素治疗中获得持久的老年保护，短暂的雷帕霉素治疗会激活肠道Paneth细胞的自噬作用。未来，要关注抗衰老干预措施中经常出现男女差异反应，进行精准抗衰老治疗。此外，传统的药物研发流程（可能）需要针对抗衰老药物研发进行调整，如动物模型、终点、监管等。部分与会嘉宾合影高端对话干细胞产业与监管程增江（主持人）：中国食品药品企业质量安全促进会副会长、同写意董事长在细胞治疗产品应用于人体治疗疾病之前，确保其安全性是毋庸置疑的。目前，干细胞研究或许存在以下几方面问题：从新药研发的商业逻辑看，若干细胞产品没有明确的注册上市路径，则相关市场主体或缺乏按照新药注册临床路径开展研究、报批的动力；从产品本身性质及研发角度看，干细胞治疗是个体化的治疗，这将导致每一批次的产品严格来讲都不通用、都不相同，与传统药物的研发、制备相比干细胞产品面临着特别的挑战。监管亦需考虑该领域的创新发展速度问题。因此，备案制作为一种替代和过渡的方法，可以使研究者先通过临床研究验证产品基本的安全、有效、稳定性，抑制干细胞治疗的乱象，再引导研究者通过临床试验走新药注册审评审批的路径走向规范。干细胞的治疗费用也是没有一个准确数字的，因为治疗方案因人而异。注重费用的同时也要选择合规的细胞中心，正规细胞中心有着严格的质量控制体系，可以保证治疗的效果和安全性。基于前沿生物技术的健康未来产业投资机遇程增江（主持人）：中国食品药品企业质量安全促进会副会长、同写意董事长张　宇：同写意CGT俱乐部理事长，中源协和CSO张　松：清松资本创始合伙人孙晓丹：歌路资本创始合伙人张苏华：中国研究型医院学会医工转化与健康产业融合专委会副主委兼秘书长庄秀丽：中国科学院长春应用化学研究所研究员，圣博玛生物创始人徐　百：纳通生物创始人、董事长• 从投资角度，最近几年越来越关注偏消费的场景，其中很重要的就是非医保场景。• 生命科学技术一定要在医学级的技术指导下实现。让真正有能力的消费者为这个需求买单，付出他愿意付出的成本，这就是一个好产品。• 有明确医疗效果的产品，和医美这些拥有很强需求的产品，是比较目前投资机构比较偏向的领域。• 跨界和越界，一定要避开幸存者偏差。• 真正的好的项目需要敏锐的眼光和对这个领域很深理解的人，甚至需要拥有数年的预见性和对行业的判断力，这也是为什么我们需要有更多复合型背景的公司合伙人、投资专家，推动技术创新、投资转化。• 中国医生在工科背景方面相对稍弱，因此需要医疗培养复合型的应用交叉人才。同时也需要培养具备企业运营能力的科学家，也就是进行跨学科人才培养。• 医美行业存在一些乱象，但随着科研进步、做高端产品的企业家们逐渐解释清楚这个科学，进入到市场的产品质量会提高，未来这个乱象逐渐会被打破。• 干细胞是维持机体器官生长和新陈代谢的动力，同时也是机体修复衰老退行性变的最重要、最基本的生物单位，是决定生命衰老的关键因素。• 干细胞抗衰老的原理是通过输注特定的干细胞，激活人体自身的“自愈功能”。• 如果亚健康时能及时补充干细胞，让它们分化成各种各样的组织器官细胞，维持好新陈代谢，将有助于我们拥有年轻态的身体与健康。写意花絮同写意执行团队合影

Researchers have discovered that turning brain immune cells into neurons successfully restores brain function after stroke-like injury in mice. These findings suggest that replenishing neurons from immune cells could be a promising avenue for treating stroke in humans. Researchers at Kyushu University have discovered that turning brain immune cells into neurons successfully restores brain function after stroke-like injury in mice. These findings, published on October 10 in PNAS, suggest that replenishing neurons from immune cells could be a promising avenue for treating stroke in humans. Stroke, and other cerebrovascular diseases, occur when blood flow to the brain is affected, causing damage to neurons. Recovery is often poor, with patients suffering from severe physical disabilities and cognitive problems. Worldwide, it's one of the most common causes for needing long-term care. "When we get a cut or break a bone, our skin and bone cells can replicate to heal our body. But the neurons in our brain cannot easily regenerate, so the damage is often permanent," says Professor Kinichi Nakashima, from Kyushu University's Graduate School of Medical Sciences. "We therefore need to find new ways to replace lost neurons." One possible strategy is to convert other cells in the brain into neurons. Here, the researchers focused on microglia, the main immune cells in the central nervous system. Microglia are tasked with removing damaged or dead cells in the brain, so after a stroke, they move towards the site of injury and replicate quickly. "Microglia are abundant and exactly in the place we need them, so they are an ideal target for conversion," says first author, Dr. Takashi Irie from Kyushu University Hospital. In prior research, the team demonstrated that they could induce microglia to develop into neurons in the brains of healthy mice. Now, Dr. Irie and Professor Nakashima, along with Lecturer Taito Matsuda and Professor Noriko Isobe from Kyushu University Graduate School of Medical Sciences, showed that this strategy of replacing neurons also works in injured brains and contributes to brain recovery. To conduct the study, the researchers caused a stroke-like injury in mice by temporarily blocking the right middle cerebral artery -- a major blood vessel in the brain that is commonly associated with stroke in humans. A week later, the researchers examined the mice and found that they had difficulties in motor function and had a marked loss of neurons in a brain region known as the striatum. This part of the brain is involved in decision making, action planning and motor coordination. The researchers then used a lentivirus to insert DNA into microglial cells at the site of the injury. The DNA held instructions for producing NeuroD1, a protein that induces neuronal conversion. Over the subsequent weeks, the infected cells began developing into neurons and the areas of the brain with neuron loss decreased. By eight weeks, the new induced neurons had successfully integrated into the brain's circuits. At only three weeks post-infection, the mice showed improved motor function in behavioral tests. These improvements were lost when the researchers removed the new induced neurons, providing strong evidence that the newly converted neurons directly contributed to recovery. "These results are very promising. The next step is to test whether NeuroD1 is also effective at converting human microglia into neurons and confirm that our method of inserting genes into the microglial cells is safe," says Professor Nakashima. Furthermore, the treatment was conducted in mice in the acute phase after stroke, when microglia were migrating to and replicating at the site of injury. Therefore, the researchers also plan to see if recovery is also possible in mice at a later, chronic phase.