Green Valley Pharmaceutical Technology participated in the brain-gut axis and AD forum to discuss the frontier of brain-gut axis research with the world

author:Youth Hebei

In April, the grass grows and the warbler flies, and the spring flowers bloom. Recently, the 4th Brain-Gut Axis and AD Forum, hosted by the Beijing Society of Neurodegenerative Diseases, was successfully held at the Pudong Shangri-La Hotel in Shanghai. Green Valley Pharmaceutical Technology actively participated, carried out in-depth exchanges with experts and scholars at home and abroad in the field of neuropsychiatric disease research, discussed the frontier research progress of the brain-gut axis, and helped expand the new connotation of discipline development.

Green Valley Pharmaceutical Technology participated in the brain-gut axis and AD forum to discuss the frontier of brain-gut axis research with the world

Meeting site

Under the chairmanship of Professor Li Yueming of Memorial Sloan-Kettering Cancer Center, Mr. Lv Songtao, Chairman of Green Valley Pharmaceutical Technology, delivered a welcome speech to more than 20,000 online and offline participants, including Professor David Holtzman, Academician of the American Academy of Sciences and the United States Academy of Sciences and Professor of Neurology at Washington University in St. Louis, Professor Sangram Sisodia, Foreign Member of the National Academy of Sciences of India and the Royal Academy of Sciences of Spain, and Director of the Center for Molecular Neurobiology at the University of Chicago. Dr. Qiong Wang from the First Affiliated Hospital of the University of Science and Technology of China and Professor Li Gan from Weill Cornell Medical College respectively discussed the sex-specific regulation of mannute sodium capsule (trade name: Jiu Phase 1 ®, code: GV-971) on amyloidosis and neuroinflammation, the role of intestinal microbiota in tau-mediated neurodegeneration, and the effect of GV-971 on the progression of AD through the regulation of innate immune activation. On behalf of Professor Geng Meiyu, the academic director of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences and the main inventor of GV-971, and his research team, Dr. Zhang Jing of the Green Valley Research Institute gave a detailed interpretation of the academic report entitled "GV-971: Present and Future"; Professor Li Yueming moderated the open discussion session, and Professor David Holtzman, Professor Sangram Sisodia, Professor Gan Li, Dr. Jing Zhang, Dr. Qiong Wang, and Dr. Jinhe Li, CEO of Green Valley Pharma Technology, had a heated discussion with the participants on the latest frontier progress of GV-971 and the future research direction of AD.

AD is not a single-cause disease, and clinical treatment should actively break through the limitation of a single target of Aβ

In his opening speech, Professor Li Yueming introduced the participants and wonderful academic topics of the conference, and pointed out that AD is not a simple "single-cause disease", and the latest genetic studies have emphasized the important role of neuroinflammation in the pathogenesis of AD. In addition, there is a certain balance in the human gut microbiota, and if this balance is broken, neurodegenerative diseases such as AD may occur.

Green Valley Pharmaceutical Technology participated in the brain-gut axis and AD forum to discuss the frontier of brain-gut axis research with the world

Professor Li Yueming

In his speech, Mr. Lv Songtao expressed his ambition and expectation to work with academia and clinical to promote the rapid development and continuous contribution of cognitive science in China. Lv Songtao said that the demand for cognitive health is exploding and has become a core challenge for human health today. The incidence of cognitive impairment represented by AD is increasing rapidly. Since its launch on December 29, 2019, Mannute Sodium Capsule has benefited more than 150,000 patients. Its unique clinical efficacy has been recognized by more and more patients and doctors. This further verifies that the mechanism of action of the brain-gut axis in the systematic treatment of AD from a holistic perspective can break through the limitations of a single target, or open up a new clinical treatment pattern for the treatment of systemic chronic systemic cognitive impairment diseases such as AD.

Green Valley Pharmaceutical Technology participated in the brain-gut axis and AD forum to discuss the frontier of brain-gut axis research with the world

Mr. Lu Songtao

There is sufficient evidence to verify the pathogenesis of the gut-brain axis, and it is promising to regulate the overall intervention of the gut-brain axis in AD

Prof. David Holtzman elaborated on the findings published by his research team and Prof. Sangram Sisodia in the prestigious journal Science. The study showed that when the intestinal microbiota is out of balance, it can alter bacterial metabolites, including short-chain fatty acids (SCFAs), affect peripheral immune cells, and then promote central nervous system inflammation, leading to tau aggregation and neurodegeneration. Short-term antibiotics or aseptic conditions can remodel or eliminate the gut microbiota and reduce its metabolites, which in turn affects the role of peripheral immune cells on central nervous inflammation and tau-mediated neurodegeneration. This study verifies the brain-gut axis mechanism of AD and other neurodegenerative diseases, provides sufficient evidence for the direct involvement of intestinal microbiota in tau pathology, and further improves the "mechanism evidence puzzle" of brain-gut axis theory in neurodegenerative diseases. Moreover, these research results also provide a detailed basic scientific basis for breaking through the limitations of single-target therapy and applying GV-971 to target the regulation of the brain-gut axis in the treatment of AD.

Green Valley Pharmaceutical Technology participated in the brain-gut axis and AD forum to discuss the frontier of brain-gut axis research with the world

David Holtzman教授

Professor Sangram Sisodia presented a series of studies on the treatment of neurodegenerative diseases, focusing on the studies conducted independently by the University of Chicago using the APPPS1-21 model and the Washington University in St. Louis using the 5xFAD model. These two independent studies both explored the effects of GV-971 on gut microbiota, Aβ deposition, and microglial phenotype, and confirmed that GV-971 targets the "gut microbiota-microglia-amyloid axis", respectively, and showed that treatment with GV-971 at the onset of Aβ deposition or after Aβ deposition has reached high levels reduces plaque pathology and neuroinflammatory features. These results validate the association between gut microbiota, neuroinflammation and AD pathology, while highlighting the potential of GV-971 to target the brain-gut axis, regulate gut microbiota, inhibit neuroinflammation, reduce Aβ deposition and treat AD. Professor Sangram Sisodia pointed out that the academic community should consider the gut microbiota as a very important foundation in neuroscience research, because the gut microbiota plays a very important role in the pathology of AD and other neurodegenerative diseases.

Green Valley Pharmaceutical Technology participated in the brain-gut axis and AD forum to discuss the frontier of brain-gut axis research with the world

Sangram Sisodia教授

Dr. Wang Qiong explained the research on GV-971 regulating innate immune activation to affect the progression of AD. Studies of the effects of GV-971 on AD-like pathology in 5xFAD mice have shown that GV-971 improves spatial learning and memory, reduces presynaptic proteins, and can inhibit the production of highly phosphorylated tau protein (p-tau), attenuate microglial activation, and have no effect on the formation of insoluble plaques. This study provides more informative evidence for GV-971 to target the gut microbiota as a new strategy for the treatment of AD. At present, the new real-world clinical study has completed the enrollment of patients, and the follow-up work will be completed in December this year, and further comprehensive analysis of clinical data will be made in the future, or more evidence of AD treatment will be obtained.

Green Valley Pharmaceutical Technology participated in the brain-gut axis and AD forum to discuss the frontier of brain-gut axis research with the world

Dr. Wang Qiong

Targeted neuroimmune interactions enhance cognitive resilience against tau disease

Professor Gan Li gave an in-depth and detailed elaboration on the role of targeted neuroimmune interactions in enhancing cognitive resilience against tau disease. Starting from the key question of "how to enhance the resistance of the aging brain to tau?", Professor Gan Li systematically sorted out a series of important research results in recent years (2018 to present), and pointed out that the cyclic guanosine monophosphate-adenosine phosphate synthetase-interferon gene stimulating factor (cGAS-STING) pathway can affect the DNA of bacteria, viruses and other microorganisms, and then produce type I interferon (IFN-I) and other inflammatory factors, thereby effectively mediating innate immune responses. Multiple studies have demonstrated that immuno-risk alleles, such as TREM2R47H and APOE4, can have an effect on cGAS-STING IFN signaling in microglia in female tau-disease mice. Specifically, activation of cGAS-STING IFN inhibits the resilient transcriptional network (MEF2C) in neurons, while inhibition of cGAS-STING IFN helps to enhance brain resistance to tau disease.

Green Valley Pharmaceutical Technology participated in the brain-gut axis and AD forum to discuss the frontier of brain-gut axis research with the world

Professor Ganli

Long-term efficacy and safety studies have shown that mannute sodium alone significantly improves the clinical symptoms of AD

Based on the interim data of the ABC clinical study, Dr. Zhang Jing interpreted the interim analysis results of the long-term efficacy and safety study of GV-971 based on the application status and future development prospects of GV-971. The results of the three treatment scales, Alzheimer's Disease Scale-Cognition (ADAS-cog), Mini-Mental State Examination (MMSE), and Activities of Daily Living Scale (ADCS-ADL), consistently showed that GV-971 improved the cognitive function and daily living ability of treatment-naïve patients who had never used standard AD treatment drugs in patients treated with GV-971 alone. Acetylcholinesterase inhibitors (AChEls) and/or N-methyl-D-aspartate (NMDA) receptor antagonists have also been shown to improve cognitive dysfunction in patients treated with GV-971 in combination with standard AD treatments.

In response to the question "Why do treatment-naïve patients respond differently to treatment with standard of care (SOC)", Dr. Jing Zhang shared a subgroup analysis of treatment-naïve patients treated with GV-971, which showed that the production of beneficial bacteria producing short-chain fatty acids (SCFAs) increased and the conditional pathogenic bacteria decreased, and in patients who received SOC, the production of conditionally pathogenic bacteria increased and the production of beneficial bacteria decreased after the combination of SOC and GV-971. In addition, the results of long-term efficacy and safety studies confirmed that GV-971 has a good safety profile, a low incidence of adverse reactions, and the severity of adverse reactions is mainly mild to moderate.

Green Valley Pharmaceutical Technology participated in the brain-gut axis and AD forum to discuss the frontier of brain-gut axis research with the world

Dr. Jing Zhang

Mannute sodium regulates the brain-gut axis in the treatment of AD in the future

In the open discussion session, Prof. Yueming Li, Prof. David Holtzman, Prof. Sangram Sisodia, Prof. Li Li, Dr. Jing Zhang, Dr. Qiong Wang, Dr. Jinhe Li and Chinese and foreign experts at the meeting had a warm and in-depth discussion and exchange on the theory of AD brain-gut axis, the mechanism of action of GV-971, its clinical application and prospects. Experts agree that the results of the long-term efficacy and safety studies of GV-971 after marketing provide strong real-world evidence for GV-971 monotherapy in AD and achieving maximum clinical value. In the prospect of future research, the experts proposed that further research should be carried out from the aspects of in-depth understanding of the working mechanism of GV-971, determination of predictive biomarkers of GV-971, increasing the sample size of clinical trials, and exploring the moderating gender differences of GV-971.

Green Valley Pharmaceutical Technology participated in the brain-gut axis and AD forum to discuss the frontier of brain-gut axis research with the world

Discussion (from left to right: Prof. Li Yueming, Prof. Gan Li, Prof. Sangram Sisodia, Prof. David Holtzman, Dr. Zhang Jing, Dr. Wang Qiong, Dr. Li Jinhe)


Cognition is the core of life and health. The brain-gut axis theory, which embodies the holistic system treatment view, is increasingly recognized as a common mechanism for many cognitive diseases. A 2017 article published in Nature stated: "There is an association between the composition of the gut microbiota and many diseases. So the gut microbiota could be the intersection of everything in the body?". As a common pathogenesis, the brain-gut axis will show therapeutic potential in more cognitive disorder diseases, and is expected to open up new ideas for the development of innovative drugs for AD. At the end of the meeting, Professor Li Yueming expressed his satisfaction with the enthusiasm and unremitting persistence of the academic and clinical medical circles for the research of the brain-gut axis, and announced the successful conclusion of the 4th Forum on the Brain-Gut Axis and AD. The grand convening of the 4th Brain-Gut Axis and AD Forum has undoubtedly built a valuable academic platform for the world's top scientists to deeply discuss the cutting-edge research on the mechanism of the brain-gut axis and the clinical treatment strategy of AD. This forum not only further enriches the treatment theory in the field of neuroscience in mainland China, broadens the research horizon of neuroscience, but also improves the overall level of clinical diagnosis and treatment of AD in mainland China. The wisdom and achievements gathered in this forum are of great significance for promoting the development of global neuroscience research.

After the meeting, the participating experts went to the Cold Spring Harbor Asian Academic Center in Suzhou to continue their participation in the Cold Spring Harbor Asia Conference. As the first overseas branch in the 100-year history of Cold Spring Harbor Laboratory, Cold Spring Harbor Asia is an important bridge connecting the world's top scientists and an important platform to promote high-level dialogue among international researchers. At the meeting, experts will further discuss the new research progress of brain-gut axis and AD. The Brain-Gut Axis and AD Forum will continue to focus on major breakthroughs in basic and therapeutic research on AD, build a platform for international scientific discussion and cooperation between experts and scholars in China and Asia, and promote cross-field and interdisciplinary communication and cooperation.

About Green Valley Pharma Technology

Adhering to the mission of "improving human cognitive health", Green Valley Pharmaceutical Technology is committed to inheriting oriental wisdom, embracing an international vision, starting from a holistic view, interpreting traditional classics with modern science and technology, promoting theoretical innovation of the brain-gut axis, developing a sugar drug research and production technology platform with the brain-gut axis as a comorbid mechanism of cognitive impairment, and building an AI cognitive health intelligent platform integrating clinical-information-scientific research-market, so as to achieve theoretical innovation. Technological innovation and product innovation have opened up a new frontier of cognitive life science research, opened up the road of original innovation for the development of China's innovative drug industry, and contributed to global patients with a cognitive health integrated solution integrating brain health diagnosis, drug and non-drug treatment, and cognitive health big data application with the regulation of the brain-gut axis comorbidity mechanism as the core.

Green Valley was founded in 1997 and is headquartered in Zhangjiang Science City, Shanghai. The treatment areas cover Alzheimer's disease, vascular dementia, Parkinson's disease, autism and other refractory diseases that fill the gap in the world. Green Valley has sugar drug production bases in Qingpu, Shanghai and Benxi, Liaoning. Through extensive cooperation, the successful development of China's original and the world's first orthogonomic drug for the systematic treatment of Alzheimer's disease, Mannute Sodium Capsule (Phase 91 ®), has been approved for marketing in China and included in the National Medical Insurance Catalog.

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