Scientists coax brain cells in mice to regenerate

CHICAGO Thu Nov 6, 2008 3:24pm EST

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CHICAGO (Reuters) - Scientists have found a way to get damaged nerve cells in the brains of mice to repair themselves, a finding that may lead to new treatments for spinal cord and brain injuries.

By turning off proteins that keep nerve cell growth in check, the researchers were able to stimulate regrowth in mice with damaged optic nerves, they reported on Thursday.

"This is the first time it has been possible to see such significant regeneration by manipulating single molecules," Zhigang He of Children's Hospital Boston, whose study appears in the journal Science, said in a statement.

A separate team found that blocking a protein that discourages cell repairs allowed nerve cells in lab dishes to regenerate.

Taken together, the findings offer leads on ways to coax damaged nerves in the brain and spinal cord to fix themselves.

The studies focused on nerve fibers called axons that carry electrical signals throughout the body.

"In your arms and legs, if these fibers are severed, they can regrow back to the muscle," said Marc Tessier-Lavigne, executive vice president of research drug discovery at biotechnology firm Genentech Inc.

"Nerve fibers in the brain and spinal cord do not regenerate. When you have a spinal cord injury, the paralysis is usually permanent," he said in a telephone interview.

"The ambition of our field is to understand why it is the fibers don't regenerate in the central nervous system."

REKINDLING GROWTH

He's team focused on a gene network called the mTOR pathway, which is very active when young nerve cells are first growing but becomes less active once nerve cells mature.

Nerve injury appears to shut down this network completely. And two proteins -- PTEN and TSC1 -- appear to be responsible for silencing this pathway, the researchers discovered.

"If we get rid of (those proteins), axons can regenerate very dramatically," He said in a telephone interview.

Mice genetically engineered to lack the proteins kept more neurons after an injury to the optic nerve than normal mice. And the mutant mice were able to grow new axons within two weeks.

He said the study suggests that blocking the proteins might rekindle the nerve cell's natural ability to grow. The team is now looking for drugs that can block the proteins.

Tessier-Lavigne and colleagues focused on a different problem -- the chemicals in the body that discourage repairs.

"Even if the nerve cell could regrow, the environment is hostile to regrowth," Tessier-Lavigne said.

He said when an axon in the spinal cord is severed, the cut end sprouts a growth cone.

"It almost looks like a little hand at the end of this cable-like structure," he said.

Tiny sensors on the growth cone pick up chemical signals. In nerves in the periphery of the body such as the finger, signals tell the axon to repair itself. But in the central nervous system, chemical signals repress growth.

Tessier-Lavigne's team found one of those signals -- a protein called PirB -- in the insulating myelin sheath that wraps around each neuron. When they blocked this myelin protein in cell cultures, they got nerve cells to grow.

Tessier-Lavigne said the hope is to use this information to make drugs that allow nerve cells in the brain and spine to repair themselves.

(Editing by Maggie Fox and John O'Callaghan)

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