Nerves damaged by brain or spinal cord injury may be regenerated by silencing natural growth inhibitors, according to a new study.
Researchers at Children's Hospital Boston conducted an experiment on mice by temporarily silencing genes that prevent mature neurons from regenerating, and causing them to recover and re-grow vigorously after damage.
Dr. Zhigang He, Associate Professor of Neurology who is also the senior author of the paper, highlights the fact that currently there is no treatment for spinal cord or brain injury because injured neurons cannot regenerate.
Studies conducted in the past, which looked at removing inhibitory molecules from the neurons' environment, have found only modest effects on nerve recovery.
However, He and Dr. Mustafa Sahin have found that re-growth is primarily regulated from within the cells themselves.
"We knew that on completion of development, cells stop growing due to genetic mechanisms that prevent overgrowth. We thought that this kind of mechanism might also prevent regeneration after injury," says He.
The researchers point out that the key pathway for controlling cell growth in neurons, called the mTOR pathway, is active in cells during development, but is substantially down-regulated once neurons have matured.
Upon injury, this pathway is almost completely silenced, presumably for the cell to conserve energy to survive.
The researchers are of the view that preventing this down-regulation may allow regeneration to occur.
During the study, He's team used genetic techniques to delete two key inhibitory regulators of the mTOR pathway, known as PTEN and TSC1, in the brain cells of mice.
The mice were subjected to mechanical damage of the optic nerve two weeks later.
Two weeks post-injury, it was observed that about 50 percent of injured neurons in the mice with gene deletions of PTEN or TSC1 survived, compared to about 20 percent of those without the deletions.
Up to 10 per cent of the surviving mutant mice showed significant re-growth of axons, the fibre-like projections of neurons that transmit signals, over long distances.
This re-growth, according to the research team, increased over time.
He says that though the current study used genetic techniques, it may be possible to accomplish the same re-growth through pharmacologic means.
"This is the first time it has been possible to see such significant regeneration by manipulating single molecules. We believe that these findings have opened up the possibility for making small-molecule drugs or developing other approaches to promote axon regeneration," adds He.
The researchers have also to determine whether such regenerated axons can restore function.
They are presently looking at axon regeneration after spinal cord injury, hoping that their approach may lead to future neural regeneration therapies.