Although victims of stroke and traumatic brain and spinal cord injuries sometimes recover through rehabilitation, they often have permanent disabilities, in part, because scar tissue and regulatory chemicals in the brain slow nerve growth, preventing nerve tissue from repairing itself. Now a treatment that has restored lost vision in lab animals appears to overcome these obstacles, allowing a mass of nerve cells to regrow after being cut.
“We think this is the basis of reconstructive brain surgery – which is something nobody has ever heard of before,” says Rutledge Ellis-Behnke, a researcher on the project and a brain and cognitive sciences researcher at MIT.
The treatment, described online this week in the Proceedings of the National Academy of Sciences and performed at MIT, Hong Kong University, and Fourth Military Medical University in China, may be available to humans in trials in as little as three years if all goes well in large-animal studies, the researchers say.
In their experiments, the researchers first cut into a brain structure that conveys signals for vision, causing the small lab animals to be blinded in one eye. They then injected a clear fluid containing chains of amino acids into the damaged area. Once in the environment of the brain, these chains, called peptides, bind to one another, assembling into nano-scale fibers that bridge the gap left by the damage. The mesh of fibers prevents scar tissue from forming and may also encourage cell growth (the researchers are still investigating the mechanisms involved).
As a result, nerve cells restored severed connections, allowing 75 percent of the animals to see well enough to detect and turn toward food. The treatment restored around 30,000 nerve connections, compared with 25-30 connections made possible in other experimental treatments, Ellis-Behnke says.
Because the treatment overcomes key obstacles to the healing of nerve tissue in stroke and traumatic brain and spinal cord injury, the researchers, as well as other experts in the field, believe it could prove to be an effective treatment for these types of nervous system damage.
“The presented data are almost too good to be true,” says Wolfram Tetzlaff, professor and associate director of the International Collaboration on Repair Discoveries (ICORD) at the University of British Columbia. “Taken at face value, these findings are simply spectacular, and could become a very useful combination with other regeneration strategies,” he says. “Future studies will show how these data will hold up.” Such studies should be designed to determine whether the treatment works with a variety of brain injuries, not just the knife cuts studied so far, Tetzlaff says.
The success of the treatment is somewhat surprising, because the chemicals that stimulate nerve growth and stem cells used in other research into nerve tissue regeneration were not used here. “They just used the peptides and the cells reconnect with the target, and then the functional behavior can be seen in the animals – that’s amazing to me,” says Tat Fong Ng, an investigator at the Harvard-affiliated Schepens Eye Research Institute in Boston.
Ng wonders whether adding such chemicals and cells to the treatment might speed growth, perhaps making it possible to reconnect distant parts of the brain separated by an injury, such as in a stroke. The researchers say this might be done by forming a path through a damaged area using minimally invasive surgery and injecting the amino acid chains, which would then assemble into the fibers. The channel would both allow nerve cells to grow and guide them to the right area.
So far, the nanofiber treatment has caused no problems, such as inflammation or aggregation of fibers, in small animals. Over a few weeks, the fibers break down and leave the body in the urine. As building blocks for proteins, the amino acids might even be used for new cell growth, the researchers say. Also, because the fibers are made of natural amino acids that the body can use, the researchers are optimistic that no reaction against them will occur in studies with large animals and humans.
Ed Tehovnik, a neuroscientist at MIT who was not involved with the work, says it has “quite a lot of promise,” adding that it “may only be the start. There could be other types of nano-agents that [the MIT researchers] develop that could promote growth even better. I see this as the beginning, not the end, which is a good thing.”
Home page image courtesy of the National Academy of Sciences. Caption: Nerve cell regrowth (in green) shows a damaged area of the brain that has been repaired.