CRISPR Gene Editing Grows New Neurons In Diseased Brains
Transferring lab grown neurons into animal brains reduces the cells’ viability — their chances of integrating well into the tissue — and the efficiency with which they can restore function. So scientists at Shanghai Research Center for Brain Science and Brain–Inspired Intelligence fashioned a method to regenerate neurons inside the brain. The method is similar to how one would revive a dying plant: by nurturing it with the right conditions for it to grow new leaves.
Building up on a previous study, Haibo Zhou, a postdoctoral researcher in Hui Yang’s lab, and colleagues, set up a method to convert non neuronal brain cells called “glia” into neurons. They did this by turning down a gene called PTBP1 in glia of different parts of the mouse brain, using the gene-editing tool CRISPR. Depending on which brain region was targeted, the glia gave rise to different kinds of neurons.
Reducing PTBP1 levels presumably reverted glia to unspecified stem cells, which adopted varied neuronal identities based on which glia were targeted and the environmental signals they received. This was evident from the team’s successful attempts at restoring two different types of neurons and alleviating the symptoms associated with the loss of each.
Parkinson’s disease occurs due to loss of dopamine-producing neurons and manifests as tremors, stiffness, and loss of balance. To test their method in rejuvenating this group of neurons, the team first got rid of them using a toxic compound in mice. The authors then converted glia into dopamine-producing neurons, and the new cells showed the same activity as their original counterparts.
This rescue was not limited to just the neuron population. It also partially restored the normal motor behavior of the animal. This is a huge step forward from drug induced alleviation of symptoms because it puts forth a more permanent solution.
The team also tackled retinal diseases caused by death of retinal ganglion cells, or RGCs, which leads to permanent blindness. Turning down PTBP1 in glia of the retina transformed them into RGCs. Astoundingly, these renewed neurons not only responded to light independently, but also sent their projections to the visual cortex correctly, restoring circuit function. This led to a partial recovery of eyesight in the treated mice.