Researchers at Pennsylvania State University in State College, PA have taken a major step forward in the search for a method to recover brain function lost through injury, stroke, or illness — for example dementia and Alzheimer’s disease.
The research, published in the journal Stem Cell Reports, describes discovery of a method for converting glial cells into neurons, using a combination of four small molecules. Neurons are the cells that the brain uses for its mental functions, and glial cells generally serve the purpose of protecting them.
The neurons generated via this new method were able to function like normal brain cells, forming networks and communicating with other parts of the brain using electrical and chemical signals.
Dr. Gong Chen, professor of biology at Pennsylvania State University, and the leader of this new research, explained that neurons are unable to regenerate after an injury. Similar to the amputation of a limb, neuron death constitutes permanent damage. However, glial cells accumulate and proliferate around damaged brain tissue. Consequently, the availability of glial cells and the ability to turn them into functional neurons may be a game changer.
Previous attempts to achieve this goal were obstructed by one of the main functions of glial cells — forming scar tissue around damaged areas of the brain in order to protect it from further injury. This scar tissue also prevents the regeneration of neurons at the injury site.
A previous study by Dr. Chen and his colleagues showed that it was possible to use glial cells known as astrocytes, and turn them into neurons. However the process was extremely complicated, and although it worked in lab settings, it could not be replicated in a clinical setting.
At that time the researchers were using a series of nine small molecules in a specific sequence to achieve the results. By experimenting with hundreds of different combinations of small molecules, the team finally discovered a formula consisting of just four of these molecules.
Jiu-chou yin, a graduate student working with Dr. Chen explained, “By using four molecules, that modulate four critical signaling pathways in human astrocytes, we can efficiently turn human astrocytes – as many as 70% – into functional neurons.”
Dr. Chen and his colleagues pointed out that gene therapy approaches to solve this problem would cost approximately $500,000 per person. With the increasing numbers of individuals suffering from strokes, dementia or Alzheimer’s disease, this represents an extreme financial burden. Moreover, since gene therapy requires extremely sophisticated techniques and expertise, it would be hard to make this approach widely available.
On the other hand, the chemical programming approach discovered by Dr. Chen and his colleagues could be distributed widely and would require no expertise, since their intention is to create a simple pill for its delivery system. The team also showed that injecting this four-drug combination directly into the hippocampus, a region of the brain responsible for memory, promoted the production of new brain cells.
The researchers are optimistic that a simple pill will be developed that will regenerate neurons and help restore lost brain function, in particular memory and learning.
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