Jeffrey Cummings教授：AD药物的发现和开发历程极为艰巨，药物开发过程中的高失败率深刻反映了AD病理生理机制的复杂性和多因素交互的特性。因此，开发能够同时作用于多个病理过程的药物成为迫切需求。在此背景下，肠脑轴理论作为新兴的研究热点，在调节AD疾病进程中展现出巨大的潜力，预示着其成为AD治疗领域的一项重要策略。

Jeffrey Cummings教授：上市后临床研究在AD药物开发中占据举足轻重的地位。相较于III期临床试验中严格的入组与排除标准，上市后临床研究纳入了患有多种全身性疾病（如心血管疾病、卒中、高血压及糖尿病）的真实世界患者群体，这些患者通常还服用包括降压药和糖尿病药物在内的多种药物，从而更贴近临床实践中所面对的真实患者情况。因此，上市后临床研究能够更准确地评估药物在真实世界患者中的疗效与安全性。

特别值得关注的是甘露特钠（GV-971）抗炎作用。当前研究表明，炎症在AD及其它多种神经系统疾病（帕金森病、血管性痴呆、创伤性脑损伤等）的发病进程中扮演着核心角色。基于此，甘露特钠等具有显著抗炎活性的药物可能在多种神经系统疾病中具有应用前景。

Post-marketing studies are extremely important in AD drug development. In Phase 3 clinical trials, we have many eligibility criteria for patients who can participate in the trial, which may not translate to the care of real-world patients. In phase 4 post-marketing studies, we include patients who have multiple systemic illnesses, such as cardiovascular disease, stroke and hypertension as well as diabetes. They are taking many medications, including anti-hypertensives and diabetic medications, and they're more representative of a real-world population. So, phase 4 studies allow us to determine the effects of drugs in patients who are more like to the real-world patients that clinicians take care of. So, it's very important that we get this kind of real-world data. Of particular importance is the anti-inflammatory effects of GV-971 or oligomannate. We increasingly know that inflammation plays a major role in Alzheimer’s disease and other types of brain disorders, such as Parkinson's disease, vascular dementia, or traumatic brain injury. So, drugs that reduce inflammation may have applications across multiple types of neurological disorders.

Jeffrey Cummings教授：甘露特钠上市后临床研究为如何在临床实践中最佳使用甘露特钠提供了丰富的新见解。根据已收集的数据，全部患者已随访至48周，部分患者甚至完成96周的随访。结果显示，接受甘露特钠单药治疗的患者在为期48周观察期结束后，其认知功能相比基线水平有显著提升，表现最佳。相比之下，接受联合疗法的患者情况稍差，即在48周的观察期内，患者病情有所发展。而仅使用常规治疗药物而未使用甘露特钠的患者，在所有治疗组中的表现最差。因此，得出结论：甘露特钠作为单药治疗时疗效最为显著。甘露特钠在联合疗法中仍然有益，且联合疗法的疗效优于未使用甘露特钠的标准治疗。 

The post-marketing studies for oligomannate have provided substantial new information about how best to use GV-971 or oligomannate in clinical practice. We have data up to 48 weeks, and for some patients, we now have data up to 96 weeks. What we can see is that patients who are on GV-971 monotherapy do best in terms of their cognitive function remaining above baseline at the end of the 48-week pure observation period. Patients who were on combination therapy did less well. So, they were declining during the 48 weeks of observation. Patients receiving only on standard of care, that is, they were receiving the usual drugs but not receiving GV-971, did the most poorly of all the treatment groups. So, what we believe is that GV-971 is functioning best when given as monotherapy. It still has benefits when given as combination therapy, and combination therapy is superior to standard of care alone without GV-971.

Jeffrey Cummings教授：阿尔茨海默病患者及家属在疾病进程中常面临诸多挑战，这源于患者认知与功能的逐步退化。临床医生需通过精准的诊断流程，系统性及神经学角度全面评估，并为患者制定最佳治疗方案。上市后临床研究表明，甘露特钠作为单药治疗时，疗效最佳。甘露特钠与标准治疗联合使用时，患者也会受益，但如果未使用甘露特钠，仅标准治疗的疗效会更差。因此，甘露特钠在联合治疗中发挥作用，但最佳使用方式为单药治疗，这一结论得到了上市后临床研究数据的支持，其中仅接受甘露特钠单药治疗的患者取得了最佳的治疗效果。

Patients with Alzheimer's disease and their families face many struggles as patients have progressive decline in their cognitive and functional abilities. The clinician must respond to this by making an accurate diagnosis, assessing the patients systemically as well as neurologically, and then making the best therapeutic choices. we've Learned from the post-marketing studies that patients do best if they are given GV-971 alone. They also benefit when GV-971 is given in combination with the standard of care, and they benefit more than with standard of care only if GV-971 is not given. So, we believe that GV-971 has a role in combination therapy. but its optimal use is as monotherapy. since those were the patients who did best in the post-marketing study.

We are just beginning a new era of microbiome medicine. We can see that the microbiome is contributing to many neurological disease processes, including Alzheimer's disease, other neurodegenerative diseases, and multiple sclerosis. We're looking for drugs that can decrease the abnormalities of the gut that occur in these disorders, to restore normal gut function and, therefore, to improve brain function. What we can see, particularly from the work in the experimental animals, is that GV-971 restores the microbiome to normal and allows reduction of inflammation in the gut and then reduction of inflammation in the brain. We think that there will be many applications across neurological disorders from anti inflammatory drugs of this type.