Pioneer of In Situ Brain Neuroregeneration Professor Gong Chen: A Decade of Perseverance, Turning Dreams into Reality

“When I was a child, my dream was to become a scientist; as an adult, I truly became one.” When speaking with Orange Fruit Bureau about why he is so devoted to scientific research,Professor Chen Gong, Jinan UniversityDescribe one’s own experience in this way.

Since elementary school, encouraged by his teachers, he planted the seed of scientific research in his heart and aspired to become a scientist. In his childhood, he believed that being a scientist meant"Creating the Unprecedented", although such an idea may seem somewhat crude in retrospect, it embodies the principle that great truths are often simple.The Key to Scientific Research Is Innovation.

Thirty years later, the child who once chewed on a pen while imagining what it meant to be a “scientist” has finally seen his dream come true. Professor Chen continues to uphold the philosophy of “creating what has never existed before,” and has successfully developedIn Situ Neural Regeneration Technology in the Brain, illuminating a beacon for the treatment of neurodegenerative diseases.

When applying to university, Chen Gong chose to major in neurophysiology at Fudan University, simply because his high school biology teacher at Yancheng Middle School, Zhao Changsheng, told him:“The 21st Century is the Century of Brain Science!”, he thus bound his scientific research career to brain science.

In 1987, Chen Gong graduated from Fudan University and joined Academician Feng Depei at the Shanghai Institute of Physiology, Chinese Academy of Sciences, to conduct neuroscience-related research, eventually earning a Ph.D. in neurobiology. He subsequently pursued postdoctoral research at Yale University and Stanford University. During his postdoctoral tenure, Chen spent nearly every day in the laboratory and published multiple papers inJoined Pennsylvania State University as a professor in 2002。

At this point, Chen Gong’s “scientist dream” began to be realized step by step.

Neural regeneration has been a defining hallmark of Chen Gong’s research career. Neurons are the fundamental functional units of the brain; when the brain suffers injury or disease, both neurons and glial cells are affected. Neurons typically undergo death or degenerative changes. Due to their inability to divide, neuronal death can result in the permanent loss of the associated brain functions.How to Regenerate a Large Number of New Neurons in the BrainIt has long been a global challenge and a problem of the century, with few breakthroughs.

Determined to tackle this century-old challenge, Professor Chen Gong secured tenure at Pennsylvania State University in 2008 and decided to expand into a new research direction, focusing on“Repairing the Brain, Benefiting Humanity”as one's motto.

In 2012, the tenth year of Chen Gong’s tenure as a professor at Pennsylvania State University, he remained deeply immersed in his laboratory work, striving to discover the “magic bullet” capable of reviving dead brain neurons.

That year’s Nobel Prizes were also quite remarkable: Mo Yan became the first Chinese citizen to win the Nobel Prize in Literature; Shinya Yamanaka and John Gurdon were awarded the Nobel Prize in Physiology or Medicine for their discovery that mature, differentiated cells can be reprogrammed into pluripotent stem cells.

Professor Shinya Yamanaka’s award-winning research also served as a wake-up call for Chen Gong: “Since transcription factors can be used to convert skin cells into stem cells, can we also directly convert glial cells into neurons within the brain using transcription factors?”

Chen Gong immediately put his plans into practice. Although he had originally prepared for a protracted effort, Lady Fortune once again smiled upon him and his team:“NeuroD1 was the second transcription factor we tested, and to our surprise, it worked on the first try.”In just two years, the team turned a bold idea into reality. Their work, “In Situ Direct Conversion of Endogenous Glial Cells into Functional Neurons in the Mouse Brain Using the Neural Transcription Factor NeuroD1,” was published online in Cell Stem Cell in late 2013, named the Best Paper of 2014, and garnered significant international attention.

Behind the luck lies decades of accumulation by Chen Gong. Prior to this, Chen Gong had specifically studied the interactions between glial cells and neurons. Additionally, he frequently engaged in discussions with researchers in the field of neuroscience, sometimes conversing for an entire day.Professor Shinya Yamanaka’s research served more as a catalyst, igniting a new era for Chen Gong in “in situ neural regeneration technology of the brain.”

In 2013, for inventing the technology of in situ neural regeneration in the brain, Gong Chen was awarded the Verne M. Willaman Chair Professorship at Pennsylvania State University. In 2015, he reported for the first time the efficient transdifferentiation of human astrocytes into neurons using a small molecule cocktail; in 2019, he reported for the first time the use of NeuroD1 gene therapy to treat stroke; and in 2020, he reported for the first time the application of in situ transdifferentiation technology to treat Huntington’s disease. Gong Chen has led his team in repeatedly charging into the uncharted territory of in situ neural regeneration in the brain.

The discovery of “in situ neural regeneration technology in the brain” brought Chen Gong widespread acclaim. He not only chaired the world’s first thematic symposium on “in vivo cellular reprogramming,” but was also invited to publish a forward-looking review article on in situ neural regeneration technology in the brain in the journal Neuron. In 2019, as Chen Gong’s scientific career was advancing by leaps and bounds, he made a decision that others found hard to believe—Resign and Return to China。

The story of his resignation dates back to 2014. At that time, Chen Gong had just published his paper on “In Situ Neuroregeneration Technology in the Brain.” Many friends around him, including faculty members from the university’s technology transfer office, advised him to establish a company and leverage this new technology to develop novel products. However, Chen Gong initially did not embrace this idea; in his view, running a company was what businessmen did, whereas he considered himself a scientist.

As research deepens,Chen Gong gradually realized that brain repair technology can truly benefit humanity only when applied in clinical practice,As the person with the deepest understanding of this new technology, Chen Gong conceived the idea of starting a business, which received strong support from his family and friends. In 2016, the Smith family provided $850,000 in angel seed funding to help Chen Gong and his wife, Xu Jie, establishNeuExcell Therapeutics, which isShenxi Biologics. Thus, the scientist who was once “reluctant” to start a business has finally embarked on the entrepreneurial journey.

As Chen Gong delved deeper into his entrepreneurial venture, he found that many investors would shake their heads at the mere mention of research into neurodegenerative diseases: “There are numerous new technologies in this field, but most have ended in failure.” After careful consideration, he believed that the reason for this phenomenon lay inThere is a vast gap between the mouse brain and the human brain, with the critical link of non-human primate brain research missing in between.

However, in the United States, primate research is subject to extremely stringent, even onerous, requirements due to animal welfare concerns and ethical considerations. To advance the clinical development of “in situ neural regeneration technology for the brain,” Chen Gong decided to resign and return to China. On the flight, Chen Gong couldn’t help but remark:“I have ‘committed’ the rest of my life to monkeys, determined to achieve brain repair in primates.”

In late 2019, Chen Gong joined the Guangdong-Hong Kong-Macao Institute of CNS Regeneration at Jinan University in Guangzhou on a full-time basis, where he established the Brain Repair Center. He has devoted himself to researching “in situ neural regeneration technology,” aiming to advance in situ neural regeneration studies from rodent models to primate models.In 2020, Gong Chen’s team published the first international study on in situ neurogenesis in the brain of a primate macaque stroke model, marking another step toward clinical translation.

News of Professor Gong Chen’s return to China spread rapidly, drawing a steady stream of investors to Jinan University to meet with him and discuss the establishment of a new Chinese entity for NeuExcell. In 2021, NeuExcell Therapeutics was formally established in China, assembling an R&D team composed of multiple Ph.D.s in neuroscience and embarking on a new entrepreneurial journey. In 2022, NeuExcell Therapeutics was recognized as one of Asia’s most promising gene therapy companies. In 2023, the company won First Prize in the National Innovation and Entrepreneurship Competition Finals and was awarded the “Asia-Pacific Gene Therapy Innovation Award” by the renowned global consulting firm Frost & Sullivan.

At this point, while dedicating himself to the study of glial cell transdifferentiation into neurons, Professor Chen Gong has also successfully transformed himself from a professor into an entrepreneur.

NeuExcell Therapeutics is now on the right track. Notably, unlike other companies, its pipeline covers nearly all neurodegenerative diseases. Chen Gong told VCBeat:“All neurodegenerative diseases, whether Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), or age-related macular degeneration, are in my view ‘diseases of neuronal death.’”

Shenxi Biotech primarily focuses on in situ neural regeneration technology in the brain.“We do not screen for targets; we focus solely on how to leverage local resources to regenerate new neurons after neuronal death, thereby restoring neurological function.”

By the end of 2020, Cai Lei had established contact with Chen Gong, making ALS research one of the key focus areas for Chen Gong’s team.In 2023, the team preliminarily established a monkey model of amyotrophic lateral sclerosis (ALS).

“Once primate studies are successful, clinical trials will be just around the corner.” However, primate studies involve lengthy cycles, with each experiment typically taking more than a year. Chen Gong stated that the efficacy of the ALS drug might become evident by the end of 2024, and if all goes well, it could enter clinical trials in 2025.

Additionally,NeuExcell Therapeutics successfully administered NeuroD1 gene therapy to a glioma patient in March 2024, marking the first such clinical application worldwide.This marks the culmination of Chen Gong’s decade-long dedication, finally transforming his 2013 pioneering academic paper on NeuroD1-mediated neural regeneration into a clinical reality.

On New Year’s Day 2024, Chen Gong set a goal to achieve “three global firsts,” namely advancing the internationally original NeuroD1 gene therapy for glioma, stroke, and Alzheimer’s disease—its three leading pipelines—into clinical trials in succession. Currently, the glioma project has successfully entered clinical trials. Next, plans are underway to complete the world’s first administration of the therapy to patients with stroke and Alzheimer’s disease, thereby moving closer to the vision of “repairing the brain and benefiting humanity.”