Protein in eye may help fight autoimmune diseases in other parts of body

November 27, 2002

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 Andrew W. Taylor, PhD, associate scientist at Schepens Eye Research Institute and senior author of the study.

Dr. Taylor 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. Taylor'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. Taylor.

Although Dr. Taylor 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. William Mather, chair of the Wadsworth Foundation Scientific Advisory Board, "Dr Taylor'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. Taylor 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. Taylor'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. Taylor'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.

ZYCOS is a privately held drug discovery and development company located in Lexington, Massachusetts. The Company has two clinical programs in progress: ZYC101a for cervical dysplasia caused by HPV, which completed a Phase 2b trial in October 2002, and ZYC300 for solid tumors in a Phase 1/2 trial. ZYCOS is using its proprietary technology platform to build a pipeline of genome-derived products designed to enhance the body's defenses against specific diseases. The Company's technologies include EPIQUEST®, an antigen discovery system; CANVAS®, a high throughput screening system that detects and catalogs protein expression in cells; BIOTOPE® gene expression vectors for rapid drug development; and GENCAP(tm) biopolymer formulations for drug delivery.

The Schepens Eye Research Institute is an affiliate of Harvard Medical School and the largest independent eye research institute in the world.

* Namba K, Kitaich N, Nishida T, and Taylor AW. Induction of regulatory T cells by the immunomodulating cytokines a-melanocyte stimulating hormone and transforming growth factor-b2. J Leuk. Biol. 2002; 72: 946-952.

**"Using the lessons of ocular immune privilege to INDUCE BENEFICIAL autoimmunity in Multiple Sclerosis and demyelinating diseases"

Schepens Eye Research Institute

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