Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Key advance reported in regenerating nerve fibers

18.02.2004


Two-pronged approach synergizes growth

Researchers at Children’s Hospital Boston and Harvard Medical School have advanced a decades-old quest to get injured nerves to regenerate. By combining two strategies – activating nerve cells’ natural growth state and using gene therapy to mute the effects of growth-inhibiting factors – they achieved about three times more regeneration of nerve fibers than previously attained.

The study involved the optic nerve, which connects nerve cells in the retina with visual centers in the brain, but the Children’s team has already begun to extend the approach to nerves damaged by spinal cord injury, stroke, and certain neurodegenerative diseases. Results appear in the February 18th Journal of Neuroscience.



Normally, injured nerve fibers, known as axons, can’t regenerate. Axons conduct impulses away from the body of the nerve cell, forming connections with other nerve cells or with muscles. One reason axons can’t regenerate has been known for about 15 years: Several proteins in the myelin, an insulating sheath wrapped around the axons, strongly suppress growth. Over the past two years, researchers have developed techniques that disable the inhibitory action of myelin proteins, but this approach by itself has produced relatively little axon growth.

The Children’s Hospital team, led by Dr. Larry Benowitz, director of Neuroscience Research, reasoned that blocking inhibition alone would be like trying to drive a car only by taking a foot off the brake. "Our idea was to step on the gas – to activate the growth state at the same time," Benowitz said. "Knocking out inhibitory molecules alone is not enough, because the nerve cells themselves are still in a sluggish state."

The researchers injured the optic nerves of rats, then used a two-pronged approach to get the axons to regenerate. To gas up the sluggish nerve cells, Dr. Dietmar Fischer, first author of the study, caused an inflammatory reaction by deliberately injuring the lens of the eye. Though seemingly harmful, this injury actually stimulates immune cells known as macrophages to travel to the site and release growth factors. As Benowitz’s lab had found previously, these growth factors activated genes in the retinal nerve cells, causing new axons to grow into the optic nerve.

To try to enhance this growth, the researchers added a gene-therapy technique. Using a modified, non-infectious virus as a carrier, they transferred a gene developed by co-investigator Dr. Zhigang He into retinal nerve cells that effectively removed the "braking" action of the myelin proteins – spurring production of a molecule that sopped these inhibitory proteins up before they could block growth.

"When we combined these two therapies – activating the growth program in nerve cells and overcoming the inhibitory signaling – we got very dramatic regeneration," said Benowitz, who is also an associate professor of neurosurgery at Harvard Medical School and holds a Ph.D. in biology/psychobiology. The amount of axon regeneration wasn’t enough to restore sight, but was about triple that achieved by stimulating growth factors alone, he said.

Benowitz’s lab will continue working with the optic nerve in hopes of restoring vision. "We have to fine-tune the system, and we have some ideas of how to do it," Benowitz said. "But then we come to another big hurdle." That hurdle is getting the nerve fibers from the eye to hook up to the correct centers in the brain in such a way that visual images do not become scrambled. "It’s a mapping problem," Benowitz said. "We have to retain the proper organization of fiber projections to the brain."

Meanwhile, he and his colleagues have begun using a similar two-pronged approach to regrow axons damaged by stroke or spinal-cord injury. They have already found a way to step on the gas – using a small molecule known as inosine to switch damaged nerve cells in the cerebral cortex into a growth state. In 2002, they reported that inosine helped stroke-impaired rats to regrow nerve connections between brain and spinal cord and partially recover motor function.


The current research was supported by the National Eye Institutes, Boston Life Sciences Inc., the German Research Foundation, and the Paralyzed Veterans of America.

Children’s Hospital Boston is home to the world’s largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults for more than 130 years. More than 500 scientists, including seven members of the National Academy of Sciences, nine members of the Institute of Medicine and nine members of the Howard Hughes Medical Institute comprise Children’s research community. Children’s is the primary pediatric teaching affiliate of Harvard Medical School. For more information about the hospital visit: www.childrenshospital.org

Aaron Patnode | EurekAlert!
Further information:
http://www.childrenshospital.org/

More articles from Life Sciences:

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>