Re: NT3 Gene Therapy for CMT1A Benefits Mice

[Guest guest]

As a biochemist , this article is very promising .... let's hope also for other

forms of CMT. This may the breakthrough that someone else mentioned, that their

Dr. had mentioned...

Sam

>

> NT3 Gene Therapy for CMT1A Benefits Mice

>

>

> by Margaret Wahl on April 21, 2010

>

> http://quest.mda.org/news/nt3-gene-therapy-cmt1a-benefits-mice

>

> Mice with a disorder resembling type 1A Charcot-Marie-Tooth (CMT1A) disease

that received a single intramuscular injection of genes for the protein

neurotrophin 3 (NT3) showed improvements in grip strength, ability to stay on a

rotating rod, and strength of nerve signals, investigators reported April 15, at

the 2010 meeting of the American Academy of Neurology, held in Toronto.

>

> Earlier studies had tested subcutaneous (under the skin) injections of the NT3

protein, in both mice and humans, and found hints of effectiveness. However, the

current study shows that muscle tissue can provide a reservoir for the NT3 genes

and secrete the NT3 protein, providing a more durable treatment, the researchers

said.

>

> Zarife Sahenk, a professor of pediatrics, neurology and pathology at Ohio

State University in Columbus, presented the findings, saying the promising

results offer potential for gene therapy for CMT1A — and possibly for other CMT

forms, of which there are about 30.

>

> About the new findings

>

> Mice with a mutation in the PMP22 gene, the same gene involved in human CMT1A,

received a single injection into an upper leg muscle of NT3 genes encased in

type 1 adeno-associated viral delivery vehicles (AAV1 vectors). The experiments

were conducted in the Gene Therapy Center at Nationwide Children's Hospital in

Columbus.

>

> NT3 is a naturally occuring protein that promotes nerve growth and survival.

>

> Twenty weeks after the injection, the investigators found the mice that

received the treatment had stronger signals from the sciatic nerve to the leg

muscles, larger lower-leg muscle fibers, better grip strength in their back legs

and better ability to stay on a rotating rod than did mice in the untreated

(control) group.

>

> Forty weeks after the treatment, the increases in nerve signals and

performance on the rotating rod were even greater.

>

> Meaning for people with CMT1A

>

> The study means that NT3 gene therapy in general, and intramuscular delivery

of the therapy in particular, has some potential for treating people with CMT1A

and possibly other types of CMT, because NT3 is thought to be good for nerve

fibers in general.

>

[Guest guest]

This was certainly surprising, but good news yesterday. From what I had talked

to Dr. Shy about I thought the whole issue with NT3 was dead.

Thanks to whoever corrected my typo. The estimated number of people with CMT

based on the estimated 2008 census is 12,160,000.

And , while most of CMT is CMT 1A, I believe that due to so many genetic

mutations, different genes will respond to arrestment in different ways. Our

individual phenotypes are all different. There is still alot that we don't know.

Gretchen

[Guest guest]

I thought we had a few human studies on NT3 already?

In a message dated 4/23/2010 11:52:02 A.M. Pacific Daylight Time,

gfijig@... writes:

NT3 Gene Therapy for CMT1A Benefits Mice

by Margaret Wahl on April 21, 2010

_http://quest.http://quest.http://quhttp://quest.http://quhttp_

(http://quest.mda.org/news/nt3-gene-therapy-cmt1a-benefits-mice)

Mice with a disorder resembling type 1A Charcot-Marie-Mice with a

disorder resembling type 1A Charcot-Marie-<WBR>Tooth (CMT1A) disease that

received

a single intramuscular injection of genes for the protein neurotrophin 3

(NT3) showed improvements in grip strength, ability to stay on a rotating

rod, and strength of nerve signals, investigators reported April 15, at the

2010 mee

Earlier studies had tested subcutaneous (under the skin) injections of the

NT3 protein, in both mice and humans, and found hints of effectiveness.

However, the current study shows that muscle tissue can provide a reservoir

for the NT3 genes and secrete the NT3 protein, providing a more durable

treatment, the researchers said.

Zarife Sahenk, a professor of pediatrics, neurology and pathology at Ohio

State University in Columbus, presented the findings, saying the promising

results offer potential for gene therapy for CMT1A — and possibly for other

CMT forms, of which there are about 30.

About the new findings

Mice with a mutation in the PMP22 gene, the same gene involved in human

CMT1A, received a single injection into an upper leg muscle of NT3 genes

encased in type 1 adeno-associated viral delivery vehicles (AAV1 vectors). The

experiments were conducted in the Gene Therapy Center at Nationwide

Children's Hospital in Columbus.

NT3 is a naturally occuring protein that promotes nerve growth and

survival.

Twenty weeks after the injection, the investigators found the mice that

received the treatment had stronger signals from the sciatic nerve to the leg

muscles, larger lower-leg muscle fibers, better grip strength in their

back legs and better ability to stay on a rotating rod than did mice in the

untreated (control) group.

Forty weeks after the treatment, the increases in nerve signals and

performance on the rotating rod were even greater.

Meaning for people with CMT1A

The study means that NT3 gene therapy in general, and intramuscular

delivery of the therapy in particular, has some potential for treating people

with CMT1A and possibly other types of CMT, because NT3 is thought to be good

for nerve fibers in general.

[Guest guest]

Hi ,

This injectible NT3 is NEW research, and so far, has only been done on mice, not

humans. We will know more about the study when it is published.

Gretchen