A two-pronged approach to start up a new drug technology company with a value of over 100 million, [new leap in productivity·power of source] anti-depressant and cure for old age

Here, in terms of antidepressant, original small molecules have entered the clinical trial application stage, which can quickly fight depression and have fewer side effects; here, in terms of treating Alzheimer's disease, new discoveries of the pathogenic mechanism can inhibit the internalization of brain cells from the source. the generation of pathogenic substances. At the Biology and Chemistry Interdisciplinary Research Center of the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, located in Zhangjiang Science City, "Pujiang Scholar" researcher Chen Yelin and his collaborators established a two-pronged research center with two relevant scientific research results that have been published in internationally renowned journals An original drug technology company for neurodegenerative diseases and antidepressants, with a start-up value of over 100 million yuan.

Following the "Strength of the Source" interview team for Shanghai's deepening of the construction of science and technology innovation center, reporters from Liberation Daily and Shangguan News today walked into the biology and chemistry interdisciplinary research center, which is directed by Yuan Junying, an academician of the National Academy of Sciences and a foreign academician of the Chinese Academy of Sciences. From antidepressants to treating Alzheimer's disease, observe the latest progress in disease mechanisms and drug development.

High-resolution NMR instrument in the Interdisciplinary Research Center for Biology and Chemistry. Photo by Xu Ruizhe

According to incomplete statistics, there are approximately 350 million people suffering from depression worldwide. Five years ago, the rapid antidepressant drug esketamine, which was approved for marketing in the United States, was regarded as a "miracle drug". It could relieve depression symptoms within two to three hours and was recognized as a breakthrough therapy for the treatment of refractory depression. and major depression with imminent risk of suicide. However, esketamine was generally used clinically as an anesthetic in the past. It has side effects such as hallucinations and addiction, and is a controlled drug.

"In fact, in the past, it was not clear where the precise target of esketamine was," researcher Chen Yelin from the Center for Interdisciplinary Research in Biology and Chemistry told reporters. When the efficacy and side effects of antidepressants come from different targets, then the two can be combined. Separate each other, take advantage of it and avoid its harm. As a result, Chen Yelin's team discovered the target mechanism of esketamine's direct action, and its side effects are not based on this target, which provides the possibility of developing rapid antidepressant drugs with lower side effects. It is reported that relevant research was published in the international academic journal "Nature Neuroscience" in September last year, which first proposed that a certain subtype of NMDA receptor mediates the rapid antidepressant activity of ketamine.

Chen Yelin has been collaborating with his colleague Researcher Zhu Jidong on cross-biological and chemical research since 2017. Based on this theory, he has developed a series of rapid antidepressant drug candidates. Preclinical studies have found that these drug candidates have far fewer side effects than esketamine. The idea of ​​this innovative new drug has won the favor of investors. Chen Yelin founded Slaptai Antidepressant Company and has completed the first round of financing of 20 million yuan. "The research and development is progressing quite smoothly." It is currently in the IND research stage before clinical trials, and related drugs are expected to officially launch clinical trials next year.

Not far from the Interdisciplinary Research Center of Biology and Chemistry, there is the Zhangjiang International Brain Imaging Center on the Zhangjiang Campus of Fudan University. Photo by Xu Ruizhe

It is also located in the laboratory of Fudan University Human Phenome Research Institute on Zhangjiang campus. Photo by Xu Ruizhe

[Precise positioning, high specificity, source blocking]

Also last year, Chen Yelin's laboratory's important new discovery on the pathogenesis of Alzheimer's disease was published in Neuron, the top journal in the field of neuroscience. Alzheimer's disease, commonly known as Alzheimer's disease, has both non-familial hereditary and familial hereditary forms. The former is common and the latter is rare. Their team elucidated that the common Alzheimer's disease risk factor "ApoE4" is similar to the pathogenic mechanism of rare Alzheimer's disease, suggesting that abnormal γ-secretase is a common cause of the disease.

The key pathological feature of patients with Alzheimer's disease is the large number of amyloid plaques in the brain. These plaques are produced by the aggregation of β-amyloid protein, and mutations in γ-secretase are involved in the production of β-amyloid protein. This research work found that the active area of ​​ApoE can be precisely located in areas with high incidence of β-amyloid lesions, inhibiting its production from the source in a highly specific manner, thereby reducing amyloid plaques. Therefore, it theoretically has the potential to treat Alzheimer’s disease. potential for Alzheimer's disease. Chen Yelin said, "We found for the first time that ApoE2 as an isomer has the strongest inhibitory activity against γ-secretase, while ApoE4 has lost this activity." The reviewer of "Neuron" believes that this is a very novel , a provocative and exciting new discovery that will lead to a rethinking of gamma-secretase and its role in Alzheimer's disease.

This original research with the potential to become a drug can guide the creation of blocking agents for Alzheimer's disease causative factors. It has also entered startup companies such as Chen Yelin for further research and development. It is worth noting that, coincidentally, the Biology and Chemistry Interdisciplinary Research Center has created three new drug technology companies with a start-up value of over 100 million through the transformation of laboratory results.

Illustration of the cryo-electron microscope room at the Interdisciplinary Research Center for Biology and Chemistry. Photo by Xu Ruizhe

Focusing on brain diseases, two lines run in parallel; monetize "paper" to benefit mankind. As the world's first scientific research institution to focus on neurodegenerative disease mechanisms and drug development based on the deep intersection of biology and chemistry, researcher Zhou Jiewen, deputy director of the Interdisciplinary Research Center, told reporters that Chinese scientists have the ability and technology to explore more treatments for neurodegenerative diseases. New mechanisms, new methods, and new drugs bring greater hope to patients around the world and the possibility of improving the quality of life.