article about uveitis and other autoimmune conditions

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Protein in eye may help fight autoimmune diseases in other

parts of body

Wadsworth foundation awards $330,000 grant to develop

future therapies for multiple sclerosis

Boston, MA †" A factor (protein) in the eye involved in the

eye's " immune privilege " has prevented and halted autoimmune eye

disease in animal models and promises to aid in preventing and

treating other autoimmune diseases, including multiple sclerosis and

diabetes, according to scientists at the Schepens Eye Research

Institute. In a study in the November issue of the Journal of

Leukocyte Biology, * the authors demonstrated that the factor alpha-

MSH, when harnessed and used as a therapeutic drug, successfully

prevented the onset of and stopped the progression of uveitis, a

sight stealing autoimmune disease. Based on this study and the basic

research leading up to it, the Schepens Eye Research Institute team

was awarded a $330, 000 grant by the Wadsworth Foundation** to

explore new therapies for multiple sclerosis last week.

" The results of our study are exciting and significant because they

confirm for the first time that this factor can be successful in the

treatment of an autoimmune disease, something that we have been

suspecting since we first found alpha-MSH in the eye, " says

W. , PhD, associate scientist at Schepens Eye Research

Institute and senior author of the study.

Dr. and his laboratory discovered alpha-MSH while

investigating immune privilege, a special property of the eye that

allows the eye to protect itself without the inflammation caused by

the body's conventional immune response to injury and infection. The

eye evolved this unique regulation of immunity because inflammation

can destroy the delicate light gathering tissues of the eye and cause

permanent vision loss. Dr. 's team discovered that alpha-MSH

helps block the inflammatory immune response by blocking conventional

T cells from mediating inflammation. In addition, the team discovered

that alpha-MSH was converting the conventional T cells into

regulatory T cells. These regulatory T cells in turn further block

the activity of other inflammatory T cells. They also, found that the

regulatory T cells suppressed immunity in a specific manner,

targeting the tissue under attack by inflammatory T cells.

The team recognized and then decided to test the potential for alpha-

MSH to prevent autoimmune diseases, which are diseases where

conventional T cells perceive a part of the body (self) as foreign.

They chose a mouse model of autoimmune uveitis. In autoimmune

uveitis, the body mounts an attack against the retina (the light

gathering tissue in the back of the eye) -- a misguided attack that

can cause serious vision loss both in animals and human beings.

Schepens scientists took T cells from similar mice without uveitis

and placed those cells in a culture with alpha-MSH and TGF-beta2,

another factor found in the eye, which enhances the action of alpha-

MSH. These T cells were specific for a self protein found in the

retina. In the culture, these conventional T cells were coaxed into

becoming " regulatory " T cells and were then injected into the mice

with the disease. On examination of the eyes of the mice, the

research team found that the severity of uveitis was significantly

reduced and in most cases, the onset of the disease was prevented.

" This technique was extremely effective in the mouse model, and we

believe that it has a great potential to work in other autoimmune

diseases by changing the immune response responsible for multiple

sclerosis or for the onset of Type 1 diabetes. " Says Dr. .

Although Dr. cautions that the exploration of the this

technique is in its early stage, if it is found to be effective in

humans it may someday offer a tissue targeted treatment for

autoimmune diseases, which are often treated with steroids that can

impact the whole body, he notes.

Says Dr. Mather, chair of the Wadsworth Foundation Scientific

Advisory Board, " Dr 's research and his initial results are

extremely exciting and we are hoping this will lead directly to more

effective therapies. We believe this is seminal work. "

Dr. has already been working with a pharmaceutical company,

Zycos, which holds the license for his alpha-MSH discoveries and is

researching gene therapies using these discoveries. The Wadsworth

Foundation hopes he will continue to explore the means to adapt

immune privilege in the eye for therapies to treat multiple sclerosis

and other demyelinating disease.

Having obtained proof of principle in his study of autoimmune

disease, the next steps in Dr. 's efforts include understanding

the behavior of the regulatory T cells and to see if it is possible

to create or recreate immune privileged tissues using the factors of

the eye. This research will be done as Dr. 's team further

studies the means to adapt immune privilege to prevent autoimmune

diseases and other undesirable immune responses like rejection of

transplanted organs.

The Wadsworth Foundation supports research in a wide range of

biological disciplines, including neuroscience, cell and molecular

biology and immunology to move advances in basic science toward

therapies and cures for Multiple Sclerosis.