Brain Glial Cells Reprogrammed into Working Neurons

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A new gene therapy can turn certain brain glial cells into functioning neurons, which could help repair the brain after a stroke or during neurological disorders like Alzheimer’s or Parkinson’s diseases, according to researchers at Penn State.

A new gene therapy can turn certain brain glial cells into functioning neurons, which could help repair the brain after a stroke or during neurological disorders like Alzheimer’s or Parkinson’s diseases, according to researchers at Penn State.

In a series of studies done in animals, the team, led by Gong Chen, a professor and Verne M. Willaman chair in Life Sciences, developed a new gene therapy to reprogram glial cells to turn into healthy, functioning neuron cells.  In addition to neurons, the human brain is composed of glial cells, which surround each neuron, help support healthy brain function, and can be activated when neurons die. Chen said each glial cells contains neural genes that are silenced, or switched off, during early brain development.

By creating a new in-vivocell conversion technology, Chen said he and his team were able to inject a neural transcription factor called NeuroD1, a protein that activates neuronal genes and silences glial genes, within injured parts of the brain to infect glial cells. NeuroD1 then binds with the glial cell’s DNA and activates the neuron genes, turning the glial cell into a functioning neuron.

“This is an economic way of internal neuroregeneration without the need to transplant external cells,” Chen said in a university press release. “Because glial cells are abundant throughout human brains, every patient is equipped with such potential for internal neuroregeneration that has not been fully realized yet.”

Chen said that in their animal studies, they were able to not only regenerate neurons with the new technique, but also restore motor and cognitive functions.

 “Our new technique is different in that it actually regenerates neurons after they’ve already died, and can be used days, weeks or months after injury.”

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While the technology has only been tested in animals, the team hopes to eventually test the technology in a clinical trial, although trials in humans may be years away. When a patient experiences an injury like a stroke, or develops a neurological disorder like Alzheimer’s, neurons in parts of the brain die, creating a decline in brain function. Chen believes that because adults do not have the ability to regenerate neurons on their own, developing a treatment to help patients make new neurons would benefit a large number of patients experiencing neurological disorders that are currently incurable.

“Neuronal loss is the common cause of these functional deficits in the brain and spinal cord,” Chen said. “Therefore, simply targeting cell signaling pathways affected by these neurodegenerative disorders without regenerating new neurons will not be most effective to restore the lost brain functions.”

Additionally, the researchers are also working on a drug therapy that converts human glial cells into neurons. The team has reported success with the drug therapy in vitro in cell cultures, and Chen said they hope to move to animal studies in vivo and eventually to help human patients.

Source: Penn State