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Stanford study first to show antibodies involved in nerve repair in injuries

June 15, 2010

Filed under: Uncategorized

In a new study conducted in mice, to be published online June 14 in Proceedings of the National Academy of Sciences, the Stanford scientists show for the first time that antibodies are critical to the repair of nerve damage to the peripheral nervous system — nervous tissue that extends outside the brain and spinal cord, such as the sciatic nerve, where circulating antibodies have access. The study also shows that some, but not all, antibodies get the job done. Harnessing those proteins’ unanticipated nurturing qualities may lead to new ways of repairing damage from stroke or spinal-cord injury, as well.

“Nobody has known why, but nerve cells in the central nervous system fail to regenerate after injury whereas those in the peripheral nervous system regenerate robustly,” said senior study author Ben Barres, MD, PhD, professor and chair of neurobiology. So his group was intrigued by one major difference between the two nervous systems: Antibodies, which are large bulky proteins, have limited access to the brain and spinal cord (these organs are surrounded by an interface called the blood-brain barrier or, in the spinal cord, the blood-spinal cord barrier), while they have ready access to the peripheral nervous system.

Nerve cells convey electrochemical impulses over long distances by means of long, tubular projections called axons. These axons are typically wrapped in an insulating layer of a fatty substance called myelin.

“After nerve injury, the degenerating myelin downstream from the injury is rapidly cleared in the peripheral, but not the central, nervous system,” said Barres. “In fact in an injured human brain or spinal cord, the degenerating myelin just sits there for the rest of the person’s lifetime. But after injury to, say, the sciatic nerve, the degenerating myelin is cleared within a week or less.”

The two first authors, Mauricio Vargas, MD, PhD, a former student in Barres’ lab, and Junryo Watanabe, PhD, a postdoctoral researcher in the lab, wondered whether antibodies to components of degenerating myelin might play a role in that clearance. The researchers obtained mutant laboratory mice that can’t make antibodies, and demonstrated that, in those mice, repair of injury to the sciatic nerve is substantially impeded, as is the removal of degenerating myelin downstream from the injury site. Simply injecting the injured mutant mice with antibodies from healthy, uninjured ones restored both myelin removal and sciatic-nerve repair capability in the mice.

While antibodies have been found to play a role in the disposal of aging red blood cells, this is the first time they’ve been implicated in injury repair, said Vargas, now in his internship at White Memorial Medical Center in Los Angeles pending the start of his residency in ophthalmology at UCLA.

What’s more, the investigators threw light on the way in which this happens. “We showed that antibodies grab onto degenerating myelin downstream from the site of the nerve injury, coating the myelin and tagging it for clearance by voracious immune cells called macrophages,” Vargas said.

The word macrophage roughly translates from Greek as “big eater.” These roving gourmands are especially prone to gobble up antibody-tagged bacteria and diseased cells. “It’s analogous to spreading cream cheese on a bagel,” said Vargas.

Using various standard laboratory tools, including special staining techniques, the study’s authors observed that macrophages do indeed chew up antibody-tagged degenerating myelin downstream from the nerve-injury site. Myelin clearance in the antibody-lacking mice was substantially enhanced when antibodies from healthy mice were provided.

Surprisingly, it made no difference whether the antibodies came from normal mice that had suffered similar injuries or mice that had suffered none. This suggests that the antibodies binding to degenerating myelin and flagging it for demolition by squads of macrophages are already present in uninjured mice, rather than summoned into service only after injury. These “off-the-shelf” natural antibodies save the week or two that it would have taken the body to generate the more sophisticated, precisely shaped antibodies that are produced in response to a particular viral or bacterial infection.

In an additional experiment, the Barres team injected the injured mice with a dose of an antibody that specifically targets a protein known to occur only on myelin. Doing so restored nerve-injury repair, whereas administering antibodies that bind to targets not associated with myelin didn’t help. This proved that not just any antibodies, but rather antibodies that associate with degenerating myelin, are the ones that expedite nerve repair in the peripheral nervous system.

It wouldn’t be helpful if naturally occurring antibodies were unable to distinguish between working and worthless myelin — this could result in debilitating autoimmune disease. But, Barres said, degenerating myelin has structural features on its surface that are quite different from those exposed to the immune system on the surface of functioning myelin.

Although these findings all involve the peripheral nervous system, they offer a tantalizing hint as to a possible way to instigate repair to damaged nerve cells in the central nervous system after, say, a stroke or spinal cord injury. “One idea,” said Barres, “would be to bypass the blood-brain barrier by delivering anti-degenerating-myelin proteins directly into the spinal fluid. We’re hoping that these antibodies might then coat the myelin, signaling to microglia — macrophages’ counterparts in the central nervous system — to clear the degenerating myelin.” That might, in turn, jump-start the regeneration of damaged nervous tissue, he added.

“This is really important, elegant work,” said Zhigang He, PhD, associate professor of neurology at Harvard Medical School whose lab focuses on the intrinsic regenerative ability of nervous tissue and who did not participate in the study but is familiar with it. “Everybody’s trying to understand what accounts for the difference between the capacities for repair in the peripheral versus the central nervous system. Now we have a possible mechanism, so we can start to think about some kind of strategy to speed up myelin clearance in the brain.”

Provided by Stanford University Medical Center

Neurologists Come Together to Tackle Charcot-Marie-Tooth

June 13, 2010

(From the University of Rochester Medical Center.)
Neurologists around the nation are working together in a nationwide study focusing on Charcot-Marie-Tooth disease, a painful nerve condition that affects more than 100,000 Americans. The team and its Inherited Neuropathies Consortium is supported with $6.25 million through the National Institutes of Health Rare Diseases Clinical Research Network for the next five years.

CMT is one of the most common genetic nerve disorders and is the most common inherited form of neuropathy, but there is no effective treatment.

“This disease can really have a severe impact on a person’s health, yet there just isn’t as much awareness about it as there is for some other conditions,” said neurologist David Herrmann, MBBCh, associate professor in the Department of Neurology at the University of Rochester Medical Center and the lead investigator for the CMT Research Network in Rochester. “Nevertheless, Charcot-Marie-Tooth can be devastating for patients.”

The project, which is based at Wayne State University, brings together experts who are learning more about the disease and searching for new treatments. Herrmann and colleagues are part of a group compiling a database of people in North America who have CMT and who have volunteered to make their information available to researchers. The team is also working to pinpoint more precisely the different genes at work in the disease and how each affects the health of patients; scientists are aware of more than three dozen gene mutations that can cause CMT.

Currently Herrmann and colleagues from Wayne State University and Johns Hopkins are conducting a study in 110 people measuring the effectiveness of high doses of Vitamin C for treating CMT. With the new funding, the expanded team plans to conduct a new study aimed at testing a potential treatment.

In late 2008 neurologists created the first diagnostic guidelines for neuropathy. Herrmann himself is also an expert in the use of skin biopsy to identify sensory neuropathies like CMT and track their progression. He is currently developing a new non-invasive technique that uses a specialized microscope to look beneath the skin to gauge the condition of a person’s nerves in the fingers, as a way to possibly eliminate the need for a biopsy in some patients.

Variety appeal to set Chantelle Lawrence free

June 4, 2010

Filed under: People — Tags: ,

Chantelle Lawrence

Chantelle Lawrence is hoping the Variety appeal will help finance her electronic wheelchair so that she can get around unassisted.


by Josephine Gillespie for The Queensland Times

At only 13, Chantelle Lawrence has already seen the inside of more hospitals than most people will in a lifetime.

Born with a rare progressive neuromuscular condition known as Dejerine-Sottas Syndrome, Chantelle has endured 10 operations, including two hip reconstructions.

The West Moreton Anglican School year nine student is among the local children who Variety Queensland hopes to assist as part of its Variety Friday Radio Appeal on River 94.9 on Friday, June 11.

Mother Kerri said her daughter has inherited the condition from her father Raymond, who through a spontaneous gene mutation was diagnosed with the same condition close to 30 years ago.

Mrs Peters said while the family had received assistance to purchase an electric wheelchair through the Medical Aids Subsidy Scheme, they still faced a gap payment of more than $700.

The Brassall resident said the family also recently had to modify their home to better accommodate their daughter’s needs.

“We have renovated the bathroom and still have to do the kitchen,” Mrs Peters said.

“It is all ongoing costs.

“Raymond had to have his hip done last year and I had heart problems.

“It all mounts up and it can be difficult.”

Mrs Peters said monetary assistance through the appeal would mean her daughter could enjoy the freedom others took for granted, such as going to class on her own unassisted.

The Queensland Times general manager Steve Portas said the QT was fully supportive of the Variety Friday Appeal.

The children’s charity supports sick, disabled and disadvantaged children.

Variety Queensland has received more than $60,000 worth of requests for support in the region.

“The Variety appeal provides assistance to quite a number of needy Ipswich families and it is a great feeling to be able to make a difference to somebody’s life,” he said.

For more information about making a donation or hosting a Variety Friday event at your school or workplace in support of local kids, phone Variety Queensland on 3367 6999 or log on to www.varietyqld.org.au.

Girl with Dejerine-Sottas receives Children of Courage award

June 1, 2010

Filed under: People — Tags: ,

From the Macedon Ranges Leader, by Barry Kennedy:

Amber Jepsen

Amber Jepsen was one of 10 children to receive a Lions Club Children of Courage award

CARLSRUHE’S Amber Jepsen has a growing set of hobbies including horse riding, playing the keyboard, card games, drawing, painting and writing.

The seven-year-old is confident she will be a famous author and knows the full dimensions of her parent’s farm because she loves taking her dog for a walk in her electric wheelchair.

Amber’s many passions come despite some crippling setbacks caused by Charcot Marie Tooth disease of which she has an even rarer strand, Dejerine Sottas.

The neurological disorder affects signals from the brain to the spine and muscles making joints and muscles loose and fragile.

The disorder has prompted a range of physical impairments and health scares with hip and ankle surgery as well as having her spine stapled.

Amber’s mother Shelley said her daughter has no concept she even has a problem.

“She has lots of friends at Newham Primary School and at home she just hangs off everything as she criss-crosses the house,” she said.

Mrs Jepsen said the family knew the Royal Children’s Hospital too well especially as her health issues spanned many specialists.

Amber’s plucky attitude was last month honoured in the Lions Club Children of Courage award under the special needs category for children who have endured lengthy periods in hospital or with pain and trauma.

Chairperson of the awards Julie Starec said all of the nominees, aged between five and 15 had attempted to overcome their obstacles and improve the quality of their lives.

Ten children were nominated this year for the region incorporating the Macedon Ranges, Melton, Sunbury and Castlemaine including Ingrid Gersbeck from Clarkefield, 8 and Shae Benfell, 5, from Riddells Creek.

Sunburys Sophie Geytenbeek,12, also received an award for her strength suffering congenital heart disease. Molly Clohessy, 9, was awarded for her resilience in treatment for Dravet Syndrome. Patty Carlyon, 13, was awarded for an inspirational battle with leukaemia and Bulla’s Nathan Smith, 14, was awarded for his achievement over coming asthma to compete at a national level in swimming.