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.

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.

KING OF PRUSSIA, Pa., June 1, 2022 /PRNewswire/ -- NeuExcell Therapeutics, a preclinical gene therapy company focusing on improving the lives of patients suffering from neurodegenerative diseases, today announced the publication of a groundbreaking manuscript in the international journal, "Developmental Neurobiology." NeuExcell Therapeutics' scientific founder, Professor Gong Chen, along with his research team at Jinan University in Guangzhou, China published a manuscript decoding the molecular mechanisms underlying NeuroD1-induced astrocyte-to-neuron conversion. The mechanisms were determined using transcriptomic analyses which uncovered critical signaling pathways and illuminated the NeuroD1-mediated gene network during the conversion of cultured human astrocytes to neurons. This work provides further support for future clinical applications of astrocyte-to-neuron (AtN) conversion. NeuExcell's founder elucidates mechanism of neuron regeneration in the brain In recent years, AtN conversion has been achieved both in vitro and in vivo by many research teams around the world, including Prof. Chen's group at Jinan University and the company he founded, NeuExcell Therapeutics. To understand the molecular mechanism of NeuroD1-induced AtN conversion, Chen's group used retrovirus to express neural transcription factor NeuroD1 in cultured human astrocytes and collected cells for transcriptome analysis at different time points after viral transduction. The team discovered that after overexpressing NeuroD1 in astrocytes for 24 hours, NeuroD1 activated many downstream transcription factors as well as other target genes, fully converting the transcriptome from an astrocytic pro a neuronal pro two weeks. Dr. Ningxin Ma, the first author of the paper, describes the conversion, "NeuroD1 expressed rapidly in astrocytes, with a hundred-fold increase as early as the first day after viral transduction. . Other NeuroD and bHLH family members involved in neural development were also elevated, suggesting that exogenous NeuroD1 can activate the expression of endogenous transcription factors in astrocytes and initiate a cascade of conversion events." Along with the activation of neural transcription factors and a series of genes related to neural development, glial genes were gradually turned off along with the conversion process. Subsequently, by analyzing the up-regulated and down-regulated genes during the process of AtN conversion, Chen's group pieced together an interaction network of the critical genes induced by NeuroD1. Their research also showed that NeuroD1 concurrently regulated several important signaling pathways including the Wnt/IGF/MAPK/Hedgehog pathway to successfully achieve conversion This study is the first transcriptome analysis of NeuroD1-induced astrocyte-to-neuron conversion, providing critical mechanistic understanding on NeuroD1-mediated conversion of astroglial cells. This work was supported by the Endowment Fund of Mr. Charles H. Smith and the start-up fund from Jinan University. View original content to download multimedia: SOURCE NeuExcell Therapeutics