Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene therapy helps functional recovery after stroke

12.09.2019

A new gene therapy turns glial cells--abundant support cells in the brain--into neurons, repairing damage that results from stroke and significantly improving motor function in mice. A paper describing the new therapy, which uses the NeuroD1 gene, appears online in the journal Molecular Therapy. Once further developed, this NeuroD1-based gene therapy could potentially be used to treat stroke, which is a leading cause of disability in the U.S., with 800,000 new stroke patients every year.

"The current treatment for stroke has a narrow time window, typically within a few hours after the occurrence of stroke," said lead author Yuchen Chen, a postdoctoral fellow at Penn State.


This is an image of neurons (red) that were converted from glial cells using a new NeuroD1-based gene therapy in a stroke-injured mouse brain.

Credit: Chen Laboratory, Penn State

"Many patients cannot receive the treatment in time and as a result, often suffer from permanent disability caused by irreversible neuronal loss. There is an urgent need to develop a new therapy to regenerate new neurons and restore lost brain functions among stroke patients."

The human brain has approximately 86 billion neurons. While mini-strokes can be tolerated, moderate stroke involving the loss of billions of neurons leaves detrimental effects that do not spontaneously recover.

"So, the critical question that is still unanswered in the neuroregeneration field is how can we regenerate billions of new neurons in a patient's brain after stroke?" said Gong Chen, professor of biology and Verne M. Willaman Chair in Life Sciences at Penn State and leader of the research team.

"The biggest obstacle for brain repair is that neurons cannot regenerate themselves. Many clinical trials for stroke have failed over the past several decades, largely because none of them can regenerate enough new neurons to replenish the lost neurons."

Gong Chen and his team pioneered a new approach to regenerate functional neurons using glial cells, a group of cells surrounding every single neuron in the brain that provide essential support to neurons. Unlike neurons, glial cells can divide and regenerate themselves, especially after brain injury.

"I believe that turning glial cells that are already present in the brain into new neurons is the best way to replenish the lost neurons," said Gong Chen. "These glial cells are the neighbors of the dead neurons in the brain and are likely to share the same ancestral cellular lineage."

Gong Chen's team previously reported that a single genetic neural factor, NeuroD1, could directly convert glial cells into functional neurons inside mouse brains with Alzheimer's disease, but the total number of neurons generated was limited.

The research team believed that this limited regeneration was due to the retroviral system used to deliver NeuroD1 to the brain. In the current study, the research team used the AAV viral system, which is now the first choice for gene therapy in the nervous system, to deliver NeuroD1 into mouse motor cortex that had suffered from stroke.

Many neurons die after stroke but surviving glial cells can proliferate and form a glial scar in the stroke areas. The AAV system was designed to express NeuroD1 preferentially in the glial cells that form these scars, turning them directly into neuronal cells. Such direct glia-to-neuron conversion technology not only increased neuronal density in the stroke areas, but also significantly reduced brain tissue loss caused by the stroke.

Interestingly, the newly converted neurons showed similar neuronal properties to the neurons that were lost after stroke. This suggests a potential impact of the local glial lineage on the converted neuronal identity.

"The most exciting finding of this study is to see the newly converted neurons being fully functional in firing repetitive action potentials and forming synaptic networks with other preexisting neurons," said Gong Chen. "They also send out long-range axonal projections to the right targets and facilitate motor functional recovery."

A separate collaborative work led by Gregory Quirk, professor at the University of Puerto Rico, further tested the NeuroD1-based gene therapy in a rat stroke model. Quirk and colleagues also found that this direct glia-to-neuron conversion technology can rescue cognitive functional deficits induced by stroke.

"Because glial cells are everywhere in the brain and can divide to regenerate themselves, our study provides the proof-of-concept that glial cells in the brain can be tapped as a fountain of youth to regenerate functional new neurons for brain repair not only for stroke but also for many other neurological disorders that result in neuronal loss," said Yuchen Chen. "Our next step is to further test this technology and ultimately to translate it into clinically effective therapies to benefit millions of patients worldwide."

###

In addition to Chen, Chen, and Quirk, the research team includes Ningxin Ma, Zifei Pei, Zheng Wu, Susan Keefe, Emma Yellin, Miranda Chen, Jiuchao Yin, Grace Lee, Yi Hu, Yuting Bai, and Kathryn Lee at Penn State and Fabricio H. Do-Monte and Angélica Minier-Toribio at the University of Puerto Rico. The research was supported by the U.S. National Institutes of Health and the Penn State Charles H. Skip Smith Endowment Fund to Gong Chen.

Media Contact

Sam Sholtis
samsholtis@psu.edu
814-865-1390

 @penn_state

http://live.psu.edu 

Sam Sholtis | EurekAlert!
Further information:
http://science.psu.edu/news/Chen9-2019
http://dx.doi.org/10.1016/j.ymthe.2019.09.003

More articles from Life Sciences:

nachricht Discovery of genes involved in the biosynthesis of antidepressant
09.12.2019 | Leibniz Institute of Plant Genetics and Crop Plant Research

nachricht Scientists have spotted new compounds with herbicidal potential from sea fungus
09.12.2019 | Far Eastern Federal University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electronic map reveals 'rules of the road' in superconductor

Band structure map exposes iron selenide's enigmatic electronic signature

Using a clever technique that causes unruly crystals of iron selenide to snap into alignment, Rice University physicists have drawn a detailed map that reveals...

Im Focus: Developing a digital twin

University of Texas and MIT researchers create virtual UAVs that can predict vehicle health, enable autonomous decision-making

In the not too distant future, we can expect to see our skies filled with unmanned aerial vehicles (UAVs) delivering packages, maybe even people, from location...

Im Focus: The coldest reaction

With ultracold chemistry, researchers get a first look at exactly what happens during a chemical reaction

The coldest chemical reaction in the known universe took place in what appears to be a chaotic mess of lasers. The appearance deceives: Deep within that...

Im Focus: How do scars form? Fascia function as a repository of mobile scar tissue

Abnormal scarring is a serious threat resulting in non-healing chronic wounds or fibrosis. Scars form when fibroblasts, a type of cell of connective tissue, reach wounded skin and deposit plugs of extracellular matrix. Until today, the question about the exact anatomical origin of these fibroblasts has not been answered. In order to find potential ways of influencing the scarring process, the team of Dr. Yuval Rinkevich, Group Leader for Regenerative Biology at the Institute of Lung Biology and Disease at Helmholtz Zentrum München, aimed to finally find an answer. As it was already known that all scars derive from a fibroblast lineage expressing the Engrailed-1 gene - a lineage not only present in skin, but also in fascia - the researchers intentionally tried to understand whether or not fascia might be the origin of fibroblasts.

Fibroblasts kit - ready to heal wounds

Im Focus: McMaster researcher warns plastic pollution in Great Lakes growing concern to ecosystem

Research from a leading international expert on the health of the Great Lakes suggests that the growing intensity and scale of pollution from plastics poses serious risks to human health and will continue to have profound consequences on the ecosystem.

In an article published this month in the Journal of Waste Resources and Recycling, Gail Krantzberg, a professor in the Booth School of Engineering Practice...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The Future of Work

03.12.2019 | Event News

First International Conference on Agrophotovoltaics in August 2020

15.11.2019 | Event News

Laser Symposium on Electromobility in Aachen: trends for the mobility revolution

15.11.2019 | Event News

 
Latest News

The Arctic atmosphere - a gathering place for dust?

09.12.2019 | Earth Sciences

New ultra-miniaturized scope less invasive, produces higher quality images

09.12.2019 | Information Technology

Discovery of genes involved in the biosynthesis of antidepressant

09.12.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>