Blind World


Uveitis.
Blinding Eye Disease; Promising New Therapy.





March 1, 2004.




A preliminary clinical trial, conducted by researchers at the National Institutes of Health (NIH), found that an investigational treatment for uveitis (pronounced yoo-vee-eye-tis) seems to have many fewer side effects than existing therapies, leading to improved quality of life for patients with this potentially blinding disease.


Accounting for an estimated 10-15 percent of blindness in the United States, uveitis is a condition in which tissues in the eye become inflamed. If not properly treated, chronic inflammation causes scarring and leads to irreversible vision loss.


Currently, people with severe uveitis must take steroids or other drugs that suppress the immune system to control the inflammation.


Unfortunately, these powerful drugs can have many serious side effects, such as kidney dysfunction, glaucoma, osteoporosis, increased blood sugar, elevated blood pressure, and weight gain.


Because their immune systems are compromised, patients must also limit contact with other people to avoid contagious illnesses. Obviously, current therapies for uveitis severely diminish a patient's quality of life.


The clinical trial results, published in a recent issue of the Journal of Autoimmunity, found that once monthly intravenous infusions with an immune therapy drug called daclizumab controlled uveitis and was well tolerated in seven of 10 patients over a four-year period.


The study authors also found initial evidence that a formulation of daclizumab that can be injected under the skin conferred similar results. This might allow patients to administer the drug to themselves at home, making the treatment even more convenient.


'Daclizumab offers the promise of a safe, well-tolerated and effective long-term therapy for uveitis. We are now in the planning stages to begin a larger clinical trial to compare standard therapies with daclizumab,' said Dr. Paul Sieving, director of the National Eye Institute (NEI), which is part of the NIH.


NEI researchers are pioneering much of the effort to better understand uveitis in order to develop safer and more effective therapies. Although the causes of uveitis vary, the majority of cases are thought to be autoimmune in nature.


Autoimmune diseases are conditions where the body's immune system attacks parts of the body. Previous laboratory studies at the NEI found that T helper cells, which normally help fight harmful bacteria and viruses, initiate an immune response in the eye. Further work observed that the T helper cells that attack the eye have large numbers of interleukin-2 (IL-2) receptors on their surface.


This receptor activates the cell and acts like an alarm bell to recruit other immune cells into the eye, resulting in sight-threatening inflammation.


In laboratory studies, NEI investigators, collaborating with researchers from the National Cancer Institute, found that daclizumab, which blocks IL-2 receptors and thereby prevents the immune response triggered by T helper cells, showed promise in treating an experimental model of uveitis.


Previously approved by the U.S. Food and Drug Administration for use in preventing organ rejection in patients receiving kidney transplants, daclizumab's safety profile is already well characterized. These factors paved the way for FDA approval to begin the present clinical trial.


Dr. Thomas Waldmann, a co-author of the current study and chief of the Metabolism Branch of the NIH's National Cancer Institute, previously discovered much of the role IL-2 receptors play in the immune system and subsequently developed daclizumab.


'I am pleased to be involved in the planning and execution of these laboratory studies and clinical trials. Daclizumab holds great promise in treating patients with uveitis,' Dr. Waldmann said.


The discovery of the central role of these T helper cells carrying large numbers of IL-2 receptors in uveitis and the potential value of daclizumab has also spurred intense research activity in other autoimmune diseases, such as multiple sclerosis and ulcerative colitis, in which similar immune mechanisms have been implicated. Preliminary results with daclizumab have also been encouraging and clinical trials are proceeding.


Dr. Robert Nussenblatt, lead author of the study and chief of the Immunology Laboratory at the NEI, said, 'Our work in uveitis has cross-pollinated several medical research fields. We are very proud that our contributions have allowed the understanding of autoimmune disease to bloom.'


The National Eye Institute (NEI) conducts and supports research that leads to sight-saving treatments and plays a key role in reducing visual impairment and blindness. The NEI is part of the National Institutes of Health (NIH), an agency of the U.S. Department of Health and Human Services.



CONTACT:


Tom Hoglund,
National Eye Institute.
301-496-4308.



MedicalNewsToday,
83 Filsham Road,
St. Leonards,
East Sussex,
TN38 0PE,
United Kingdom.

Tel: (+44) (0) 1424 434208,
Fax: (+44) (0) 1424 716516.



Copyright 2003 Christian Nordqvist.




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