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New Treatment for Eye Disease Reduces Need for Strong Drugs

May 27, 1997

Researchers at the National Institutes of Health (NIH) have discovered a substance that allows people with uveitis, a potentially blinding eye disease, to stop or reduce the need for powerful drugs. A paper detailing these findings is published in the May 1997 issue of the American Journal of Ophthalmology.

Uveitis is a severe eye inflammation that affects children and young adults and is responsible for about 10 percent of visual impairment in the United States. Standard medical treatment has included strong steroids and immunosuppressive drugs that block the immune system and can cause serious and unpleasant side effects in the eye and other parts of the body. Researchers at the National Eye Institute (NEI), part of the NIH, found that a purified protein, called the retinal S-antigen, given orally to a small group of people with uveitis, allowed them to be weaned off these standard treatment drugs more readily than when given a placebo. Patients experienced no side effects from the new treatment.

“These findings are significant because the new treatment may allow people with uveitis to stop taking strong drugs sooner than before,” said Carl Kupfer, MD, director of the NEI. “The drugs now used as standard treatment for uveitis, while often effective, can cause decreased kidney function, cataracts, glaucoma, and brittle bones. Doctors now have to juggle their patients’ standard medication dosage to help avoid these serious problems.”

Scientists discovered that the patients receiving only the purified S-antigen were able to taper off their standard uveitis medications more successfully than three other groups given either a retinal antigen mix, the purified S-antigen plus the retinal antigen mix, or a placebo. At the end of the study, some patients returned to their standard uveitis medication, while others continued to take only the S-antigen protein and were closely followed for signs of a recurrence.

The protein used in the study was derived from animal retinas. “We knew that we only had a limited amount of this material available to us,” said Robert Nussenblatt, MD, director of Intramural Research at the NEI and the study’s principal investigator, “so we had to adjust the dose given. However, using laboratory techniques, we can now produce larger amounts of this substance. Researchers at the NEI will soon conduct another small study to determine the optimal dosage of the S-antigen protein.”

Once this study is completed, NEI plans to conduct a larger clinical trial to fully test the effectiveness of this new treatment.

Dr. Kupfer said that these initial findings provide an excellent example of “lab-to-bedside” research. “There is no better place than the intramural program at the NIH to first conduct the laboratory research and then quickly apply the findings to a small group of patients before large-scale testing,” he said. “This study sets a standard for this type of research and serves as a model for future studies.”


Treatment of Uveitis by Oral Administration of Retinal Antigens

The “Treatment of Uveitis by Oral Administration of Retinal Antigens” was a randomized, controlled clinical trial to evaluate the effect and safety of the oral administration of retinal antigens on uveitis. The study was conducted at the National Institutes of Health clinical center in Bethesda, Maryland.

A total of 45 uveitis patients were involved. Patients were dosed through an oral tolerance therapy protocol. Oral tolerance therapy controls disease by using the body’s natural defenses against the immune system, helping to save healthy tissue from immune system damage. Oral tolerance delivers specific proteins to tissues under attack from disease by getting drugs through the digestive system and into the blood stream without toxicity or significant side effects. Dosing initially consisted of oral medication three times a week for the first five weeks of the study. However, because of the difficulty in making the S-antigen protein, which comes from the retina, dosing was changed to once a week for the study’s final three weeks.

Patients were given either:

  • The S-antigen protein;
  • A retinal antigen mix;
  • A combination of the S-antigen protein and a retinal antigen mix; or
  • A placebo.

Researchers found that a purified protein, called the retinal S-antigen, given orally to people with uveitis, allowed them to be weaned off these standard treatment drugs more readily than when given a placebo. It was also noted that when the dosing was reduced from three times a week to once a week, some patients had a recurrence of uveitis.

There were two surprising findings in the study:

The group that was fed the retinal antigen mix had poorer results than those receiving the placebo; and The group receiving the combination of the S-antigen protein and retinal antigen mix yielded results similar to those receiving the placebo. Researchers had hoped that this combination group might yield results better than the placebo group and similar to those receiving solely the S-antigen protein.

Because the S-antigen protein can be produced in the laboratory and will become available for clinical use, researchers at the NEI hope to soon conduct another small study to determine the needed dosage. Autoimmune Inc., a public company located in Massachusetts, is developing the retinal S-antigen through a Cooperative Research and Development Agreement with the NEI.

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  • Nussenblatt RB, Gery I, Weiner HL, Ferris FL, Shiloach J, Remaley N, Perry C, Caspi RR, Hafler DA, Foster CS, Whitcup SM. Treatment of Uveitis By Oral Administration of Retinal Antigens: Results of a Phase I/II Randomized Masked Trial. Am J Ophthalmol. 1997 May. PubMed