$420,000 Grant for CMT Netrin-1 Research by Thien Nyguyen at 's Hopkins

[Guest guest]

http://www.mda.org/research/gaag/2010/fall/

(photo at link)

MDA has awarded a research grant totaling $420,000 over three years to Thien

Nguyen, assistant professor in the department of neurology at s Hopkins

University School of Medicine in Baltimore. The new funds will help support

Nguyen's research into the breakdown of peripheral nerves (nervous tissue that

connects the spinal cord with muscles and sensory organs) in Charcot-Marie-Tooth

disease (CMT).

Degeneration of the axons (the long fibers that carry signals from nerve cell

bodies to muscle) is a hallmark of type 1 CMT and is the primary determinant of

the severity of symptoms in people with the disease. It follows that prevention

of axonal degeneration should improve clinical outcomes for people with CMT1.

The same principle also should be applied to other types of CMT, Nguyen noted.

In previous studies, Nguyen and colleagues have determined that mutations in

genes for myelin-making cells called " Schwann cells " can lead to mutant Schwann

cells that may instruct axons to degenerate through certain specific signaling

molecules that normally promote stability and survival, including one called

myelin-associated glycoprotein (MAG). Study results out of Nguyen's lab have

suggested that another signaling molecule, called netrin-1, may play an

important role in axonal survival in CMT, making it a potential therapeutic

target.

The investigators will determine whether increasing netrin-1 activity might

prevent axonal degeneration in cell culture and in a research mouse model.

Findings from Nguyen's work could reveal the potential therapeutic benefit of

netrin-1 and lead to its development as a neuroprotective therapeutic for CMT.

" In theory, results from the project also could be expanded to axonal

degeneration even without demyelination, " Nguyen said. " Thus, there could be

applicability to many of the neurodegenerative disorders covered by MDA. "

[Guest guest]

I thought axonal was related to CMT2 and CMT1 was myelin?????

Jackie

On Feb 7, 2011, at 7:15 PM, -owner wrote:

> http://www.mda.org/research/gaag/2010/fall/

>

> (photo at link)

>

> MDA has awarded a research grant totaling $420,000 over three years

> to Thien Nguyen, assistant professor in the department of neurology

> at s Hopkins University School of Medicine in Baltimore. The new

> funds will help support Nguyen's research into the breakdown of

> peripheral nerves (nervous tissue that connects the spinal cord with

> muscles and sensory organs) in Charcot-Marie-Tooth disease (CMT).

>

> Degeneration of the axons (the long fibers that carry signals from

> nerve cell bodies to muscle) is a hallmark of type 1 CMT and is the

> primary determinant of the severity of symptoms in people with the

> disease. It follows that prevention of axonal degeneration should

> improve clinical outcomes for people with CMT1.

>

> The same principle also should be applied to other types of CMT,

> Nguyen noted.

>

> In previous studies, Nguyen and colleagues have determined that

> mutations in genes for myelin-making cells called " Schwann cells "

> can lead to mutant Schwann cells that may instruct axons to

> degenerate through certain specific signaling molecules that

> normally promote stability and survival, including one called myelin-

> associated glycoprotein (MAG). Study results out of Nguyen's lab

> have suggested that another signaling molecule, called netrin-1, may

> play an important role in axonal survival in CMT, making it a

> potential therapeutic target.

>

> The investigators will determine whether increasing netrin-1

> activity might prevent axonal degeneration in cell culture and in a

> research mouse model.

>

> Findings from Nguyen's work could reveal the potential therapeutic

> benefit of netrin-1 and lead to its development as a neuroprotective

> therapeutic for CMT.

>

> " In theory, results from the project also could be expanded to

> axonal degeneration even without demyelination, " Nguyen said. " Thus,

> there could be applicability to many of the neurodegenerative

> disorders covered by MDA. "

>

>

[Guest guest]

Hi Jackie,

Axonal really refers to the makeup of the entire nerve in CMT. This is why

people with CMT have such different phenotypes (expressions, i.e., symptoms.

This researcher determined that genes for making myelin (the wrapping around the

nerve (what we know as type 1) - also called " Schwan cells " leads to MUTANT

Schwan Cells that are telling the Axons (nerves in general) to degenerate. In

other words, a mutant gone very wrong.

His lab has worked with MAG (myelin associated glycoproteins)which give

stability and survival to the entire axon (nerve) They are a type of

nerve-signaling to the nerve/muscle synapse.

Now he's working on Netrin-1, another nerve signaling molecule, which suggests

control of it may be a potential way to target therapies for CMT.

So far it has been all work with cell cultures in the laboratory. Next step is

to test Netrin-1 in a mouse model. His theory is that harnessing Netrin may

develop a neuroprotective therapy for all of CMT because results may be

expanded into axonal degeneration even without demyelination, " ( what we know as

type 2) Nguyen said.

Gretchen

>