NeuroD1 will be tested to restore lost neurons in a nonhuman primitive model of Alzheimer's disease.
Neurogenic differentiation 1 (NeuroD1) is a transcription factor of the NeuroD type. It is encoded by the human gene NEUROD1. It regulates the expression of the insulin gene and mutations in this gene lead to type II diabetes.
Who's working on it
Several scientists from Chen Laboratories have discovered that NeuroD1 converts reactive glial cells into functional neurons in the mouse brain.
There were three articles, one in 2014 by Guo and his colleagues. They had indicated that a single transcription factor, NeuroD1, could reprogram astrocytes into neurons, providing a potential way to reconstruct neurons in the late stages of the disease.
This year, Chen announced that NeuroD1 had restored function after a stroke in mice and non-human primates after splicing into an AAV9 vector and injected into the brain.
And another article was submitted by Ge and his colleagues. Researchers are now thinking of using this strategy (NeuroD1 to restore neurons and other cells) in Alzheimer's disease.
How does NeuroD1 work?
Gong Chen and his colleagues believe that: "One reason that so many Alzheimer's trials have failed may be that too many neurons have already been lost."
NeuroD1 did this by creating not only new neurons, but also astrocytes, as it encourages astrocytes to divide and differentiate. The new astrocytes seemed to attract new blood vessels. "Essentially, we're regenerating new neural circuits," Chen said.
Could AAV-NeuroD1 work against Alzheimer's disease?
Chen and his colleagues have tried it in 5xFAD mice (an animal model with Alzheimer's disease). "We have regenerated millions of new neurons throughout the brain," Chen said. The neurons survived for at least eight months, while the number of reactive astrocytes decreased. AAV vector-treated mice remember better and find a hidden platform in an aquatic labyrinth more rapidly than untreated control mice.
Chen's team is currently testing the vector in a model of Alzheimer's disease in non-human primates in China.
And for ALS?
Chen hopes the strategy using NeuroD1 with viral load administration will also work in other diseases. His team has previously tested that AAV-NeuroD1 vectors restore motor neurons throughout the spinal cord and improve motor skills when injected into the spinal cord of mice carrying the G93A SOD1 mutation.
