Advertisement
Ingenuity
Ingenuity

New Target for Myelin Repair

Researchers identify a receptor that causes the degeneration of myelin coating around nerve cells, pointing to a potential new therapy for multiple sclerosis patients.

By | July 4, 2011

Myelinated neuronELECTRON MICROSCOPY FACILITY, TRINITY COLLEGE

Blocking a death receptor causes damaged myelin, the protective coating surrounding nerve cells, to repair itself, according to a study published Sunday (July 3) in Nature Medicine. The finding suggests that drugs targeting the receptor could help treat multiple sclerosis by reversing the myelin damage characteristic of the disease.

“Showing remyelination, as they do in vivo and in vitro, is a pretty cool result,” said Richard Ransohoff, a Cleveland Clinic neuroscientist who was not involved in the work. The new receptor is a novel first step in potentially repairing damaged nerves of multiple sclerosis patients, he said.

Current multiple sclerosis drugs slow the disease’s progression by quieting the inflammatory response of the immune system, which attacks the myelin surrounding nerve cells and kills oligodendrocytes, brain cells that make and repair myelin. Without their myelin, nerve cells gradually lose their ability to send electrical signals. But because they suppress the immune response, these drugs make patients more susceptible to rare infections such as viral brain inflammation and diseases such as leukemia.

They also cannot undo existing damage, leading scientists to seek out approaches that stimulate the growth of new myelin or the restoration of existing myelin. Though research has identified several candidate molecules that promote myelin survival, none have yet proven to do so successfully in patients.

Sha Mi, a cell biologist at the Biogen Idec, a Boston biotech company, and her colleagues were studying a multiple sclerosis drug candidate that promotes oligodendrocyte survival when they discovered that a molecule called the death receptor 6 (DR6) kills the brain cells. In 2009, the same receptor was implicated in neuronal cell death in Alzheimer’s disease, binding a precursor to the amyloid beta protein and initiating a cascade that triggers neurons to self-destruct.

To determine whether inhibiting the receptor could fuel new cell growth, the researchers first used a detergent to destroy the myelin sheaths in rat neurons, then blocked the DR6 receptor with an antibody. Sure enough, the treatment kept oligodendrocytes alive and spurred their growth and maturation, which in turn repaired the damaged myelin sheaths, Mi said.

Targeting DR6 also seemed to quiet an overactive immune response. In rats with experimental autoimmune encephalitis (EAE), an inflammatory disease used to model multiple sclerosis, inhibiting the receptor resulted in a noticeable improvement of the rats’ symptoms.  “If we are blocking DR6, we can potentially block inflammation as well as blocking cell death,” Mi said.

The findings suggest that targeting DR6 could eventually lead to new multiple sclerosis drugs that repair damaged myelin. But the anti-inflammatory effects of blocking the receptor could be a double-edged sword, because as with the current MS drugs, suppressing the immune system can have unintended consequences, said neuroscientist Bruce Trapp of the Cleveland Clinic, who did not participate in the research.  “The market is filled with anti inflammatory drugs that are doing a good job,” he said. “But you cannot get too aggressive because you get very serious side effects.”

S. Mi, et. al, "Death receptor 6 negatively regulates oligodendrocyte survival, maturation, and myelination," Nature Medicine, doi:10.1038/nm.2373, 2001.

 

 

Add a Comment

Avatar of: You

You

Processing...
Processing...

Sign In with your LabX Media Group Passport to leave a comment

Not a member? Register Now!

LabX Media Group Passport Logo

Comments

Avatar of: Michael Godfrey MBBS

Anonymous

July 5, 2011

Aiming at repairing the damage is laudable but preventing it would be more cost-effective. Notably, in both the animal and the human research there is sufficient published literature to implicate eminently treatable environmental factors with especially mercury being a prime suspect. Dr. Hans Nieper, was Europe's most renown 20th century MS doctor who successfully helped many thousands of patients. His patients always had dental amalgam replacement with demonstrable benefits.

Avatar of:

Posts: 0

July 5, 2011

Aiming at repairing the damage is laudable but preventing it would be more cost-effective. Notably, in both the animal and the human research there is sufficient published literature to implicate eminently treatable environmental factors with especially mercury being a prime suspect. Dr. Hans Nieper, was Europe's most renown 20th century MS doctor who successfully helped many thousands of patients. His patients always had dental amalgam replacement with demonstrable benefits.

Avatar of:

Posts: 0

July 5, 2011

Aiming at repairing the damage is laudable but preventing it would be more cost-effective. Notably, in both the animal and the human research there is sufficient published literature to implicate eminently treatable environmental factors with especially mercury being a prime suspect. Dr. Hans Nieper, was Europe's most renown 20th century MS doctor who successfully helped many thousands of patients. His patients always had dental amalgam replacement with demonstrable benefits.

Avatar of:

Posts: 0

July 6, 2011

Fine, except my wife had all her mercury amalgam filings replaced twelve years ago, with no discernible effect on the course of her MS.  And what would Mr Godfrey have her and the millions who have secondary MS do?  Jump off a bridge?  The true disability of MS comes later in the disease and it strikes many who are in the prime of life and their professions.  Surely they also deserve some consideration and research focus?  I have no idea who Dr. Nieper is or was, but had his approach been as effective as the writer claims, I find it hard to believe that cost-conscious European public health systems would not have adopted that methodology.  That they did not can hardly be seen as part of a vast shadowy conspiracy, can it?

The Holy Grail of MS research has become a hunt for a way to repair myelin and neuron damage.  It would be nice if we could always diagnose MS before it caused lasting damage, but that is only rarely the case.  To write off the millions who have permanent damage would be to ignore the very real personal, social and financial cost of such disabilities.

Avatar of:

Posts: 0

July 6, 2011

Fine, except my wife had all her mercury amalgam filings replaced twelve years ago, with no discernible effect on the course of her MS.  And what would Mr Godfrey have her and the millions who have secondary MS do?  Jump off a bridge?  The true disability of MS comes later in the disease and it strikes many who are in the prime of life and their professions.  Surely they also deserve some consideration and research focus?  I have no idea who Dr. Nieper is or was, but had his approach been as effective as the writer claims, I find it hard to believe that cost-conscious European public health systems would not have adopted that methodology.  That they did not can hardly be seen as part of a vast shadowy conspiracy, can it?

The Holy Grail of MS research has become a hunt for a way to repair myelin and neuron damage.  It would be nice if we could always diagnose MS before it caused lasting damage, but that is only rarely the case.  To write off the millions who have permanent damage would be to ignore the very real personal, social and financial cost of such disabilities.

Avatar of: Arthur

Anonymous

July 6, 2011

Fine, except my wife had all her mercury amalgam filings replaced twelve years ago, with no discernible effect on the course of her MS.  And what would Mr Godfrey have her and the millions who have secondary MS do?  Jump off a bridge?  The true disability of MS comes later in the disease and it strikes many who are in the prime of life and their professions.  Surely they also deserve some consideration and research focus?  I have no idea who Dr. Nieper is or was, but had his approach been as effective as the writer claims, I find it hard to believe that cost-conscious European public health systems would not have adopted that methodology.  That they did not can hardly be seen as part of a vast shadowy conspiracy, can it?

The Holy Grail of MS research has become a hunt for a way to repair myelin and neuron damage.  It would be nice if we could always diagnose MS before it caused lasting damage, but that is only rarely the case.  To write off the millions who have permanent damage would be to ignore the very real personal, social and financial cost of such disabilities.

Avatar of: Bldeagle@cox.net

Anonymous

July 8, 2011

I'd be thrilled if they were able to stop progression of, or repair the myelin sheath. I'd be in line for clinical trials. The worst possible scenario(PML) is already a game of Russian roulette with the use of Tysabri.

Avatar of:

Posts: 0

July 8, 2011

I'd be thrilled if they were able to stop progression of, or repair the myelin sheath. I'd be in line for clinical trials. The worst possible scenario(PML) is already a game of Russian roulette with the use of Tysabri.

Avatar of:

Posts: 0

July 8, 2011

I'd be thrilled if they were able to stop progression of, or repair the myelin sheath. I'd be in line for clinical trials. The worst possible scenario(PML) is already a game of Russian roulette with the use of Tysabri.

Avatar of:

Posts: 0

August 27, 2011

I fully agree as repairing the nerve sheaf is of paramount importance. This is precisely what Hans Nieper achieved with his unique Mg/Ca EAP mineral transporters many years before science caught up with metallothionines. A retired and edentulous nun with a 25 year history of MS and totally wheelchair-bound for 18 years consulted me 15 years ago. A year after starting Nieper's intravenous and oral protocols Sister Celline was able to leave the nursing home and has been self-supporting ever since. She walked up the stairs to my clinic on her 70th birthday and was later filmed by NZ TV.
The potentially vast medico-legal implications of dental amalgam have so far precluded any establishment recognition of harm although the biomedical and scientific literature is now at long last forcing the issue.  

Avatar of: Godfreymedical

Anonymous

August 27, 2011

I fully agree as repairing the nerve sheaf is of paramount importance. This is precisely what Hans Nieper achieved with his unique Mg/Ca EAP mineral transporters many years before science caught up with metallothionines. A retired and edentulous nun with a 25 year history of MS and totally wheelchair-bound for 18 years consulted me 15 years ago. A year after starting Nieper's intravenous and oral protocols Sister Celline was able to leave the nursing home and has been self-supporting ever since. She walked up the stairs to my clinic on her 70th birthday and was later filmed by NZ TV.
The potentially vast medico-legal implications of dental amalgam have so far precluded any establishment recognition of harm although the biomedical and scientific literature is now at long last forcing the issue.  

Avatar of:

Posts: 0

August 27, 2011

I fully agree as repairing the nerve sheaf is of paramount importance. This is precisely what Hans Nieper achieved with his unique Mg/Ca EAP mineral transporters many years before science caught up with metallothionines. A retired and edentulous nun with a 25 year history of MS and totally wheelchair-bound for 18 years consulted me 15 years ago. A year after starting Nieper's intravenous and oral protocols Sister Celline was able to leave the nursing home and has been self-supporting ever since. She walked up the stairs to my clinic on her 70th birthday and was later filmed by NZ TV.
The potentially vast medico-legal implications of dental amalgam have so far precluded any establishment recognition of harm although the biomedical and scientific literature is now at long last forcing the issue.  

Follow The Scientist

icon-facebook icon-linkedin icon-twitter icon-vimeo icon-youtube
Advertisement
RayBiotech
RayBiotech

Stay Connected with The Scientist

  • icon-facebook The Scientist Magazine
  • icon-facebook The Scientist Careers
  • icon-facebook Neuroscience Research Techniques
  • icon-facebook Genetic Research Techniques
  • icon-facebook Cell Culture Techniques
  • icon-facebook Microbiology and Immunology
  • icon-facebook Cancer Research and Technology
  • icon-facebook Stem Cell and Regenerative Science
Advertisement
Hamamatsu
Hamamatsu
Advertisement
The Scientist
The Scientist
Life Technologies