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Simple treatment using four small molecules converts human astrocytes – a type of common nervous system cells – into new neurons, which develop complex structures after four months, as shown. Credit: Gong Chen Lab, Penn State
A simple badtail of drugs that converts neighboring cells of damaged neurons into new functional neurons could potentially be used to treat stroke, Alzheimer's disease and brain damage. A team of Penn State researchers has identified a set of four, if not three, molecules that can convert glial cells – which normally provide support and isolation to neurons – into new neurons. An article describing the approach appears online in the newspaper Stem Cell Reports February 7, 2019.
"The biggest problem for brain repair is that neurons do not regenerate after brain injury because they do not divide," said Gong Chen, professor of biology and Verne M. Willaman Chair in Science. of life at Penn State, and leader of the research team. "In contrast, glial cells, which congregate around a damaged brain tissue, can proliferate after brain injury.I think turning glial cells close to dead neurons into new neurons is the best way to restore functions." neurons lost. "
Chen's team had already published research describing a sequence of nine small molecules capable of directly converting human glial cells into neurons, but the large number of molecules and the specific sequence required to reprogram the glial cells complicated the transition. towards a clinical treatment. In the current study, the team tested various numbers and combinations of molecules to identify a simplified approach to reprogramming astrocytes, a type of glial cell, into neurons.
"We identified the most effective chemical formula among the hundreds of drug combinations we tested," said Jiu-Chao Yin, a graduate student in Pen State biology, who identified the ideal combination of small molecules. "By using four molecules that modulate four critical signaling pathways in human astrocytes, we can efficiently transform human astrocytes – up to 70% – into functional neurons."
The neurons obtained by chemical conversion can survive more than seven months in a culture dish in the laboratory. They form robust neural networks and send out chemical and electrical signals, as do normal neurons in the brain.
The use of three small molecules instead of four also results in the conversion of astrocytes into neurons, but the conversion rate drops by about 20%. The team also tried to use only one of the molecules, but this approach did not induce conversion.
Chen and his team had previously developed a gene therapy technology to convert astrocytes into functional neurons, but because of the excessive cost of gene therapy – which can cost a patient half a million dollars or more – the cost of the therapy is high. team pursued more economical approaches. convert glial cells into neurons. The delivery system of gene therapies is also more complex, requiring the injection of viral particles into the human body, while the small molecules of the new method can be synthesized chemically and packaged in a pill.
"The most important benefit of the new approach is that a pill containing small molecules could be widely distributed around the world, even in rural areas without an advanced hospital system," Chen said. "My ultimate dream is to develop a simple medication delivery system, such as a pill, that can help patients around the world suffer from stroke and Alzheimer's disease." to regenerate new neurons and restore their lost learning and memory capabilities. "
The researchers acknowledge that many technical problems still need to be resolved before they can create a drug using small molecules, including the specificities of packaging and drug delivery. They also plan to study the potential side effects of this approach in future studies to develop the safest drugs. Nevertheless, the research team is convinced that this combination of molecules has promising implications for future drug therapies for the treatment of people with neurological disorders.
"Our years of effort to discover this simplified medication formula are bringing us closer to achieving our dream," Chen said.
This article has been republished from materials provided by Penn State. Note: Content may have changed for length and content. For more information, please contact the cited source.
Reference: Jiu-Chao Yin, et al. Chemical conversion of human fetal astrocytes into neurons by modulation of multiple signaling pathways. Stem Cell Reports. (2019) DOI: https://doi.org/10.1016/j.stemcr.2019.01.003
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