PITTSBURGH, Aug. 28 - Gamma globulin, a type of antibody isolated from blood samples that used to be routinely given to health care workers and international travelers to protect them from infectious diseases, is a highly effective treatment for pinkeye with little apparent toxicity, according to a study by researchers at the University of Pittsburgh School of Medicine. The results of the study, being published in the September 1 issue of the journal Investigative Ophthalmology and Visual Science and available online now, have significant implications for the treatment and prevention of eye diseases caused by adenovirus infections, such as conjunctivitis.
Conjunctivitis, commonly known as pinkeye, is an inflammation of the conjunctiva, the clear membrane that covers the white part of the eye and the inner surface of the eyelids. Although typically a mild, self-limiting disease in children and adults, newborns are particularly susceptible to pinkeye and can be more prone to serious health complications, even blindness, if it goes untreated. The most common cause of conjunctivitis is adenovirus infection. Unfortunately, current treatments for conjunctivitis are not specifically targeted to the virus, and, presently, there is no FDA-approved therapy for the treatment of adenoviral-mediated eye infections.
In the study, led by Andrea Gambotto, M.D., assistant professor of surgery, University of Pittsburgh School of Medicine, the researchers investigated the antiviral activity of gamma globulin (Ig) on human "wild-type" adenovirus as well as adenovirus subtypes isolated from patients diagnosed with viral eye infections. Specifically, they investigated the ability of Ig to neutralize these various adenovirus strains in both cell cultures infected with adenovirus and in rabbits with conjunctivitis.
In the cell culture (in vitro) studies, less than 10 milligrams per milliliter (mg/ml) of Ig significantly neutralized all of the wild-type strains of adenovirus, and the same concentration of Ig also neutralized almost 90 percent of the various adenovirus subtypes isolated from patients with eye infections.
In the animal (in vivo) studies using topical Ig, all of the animals tested tolerated the Ig extremely well, without displaying any irritation even at high dosages. More importantly, Ig neutralized adenovirus at least as well as cidofovir, another antiviral drug that proved to be a potent inhibitor of adenovirus eye infections in early trials but was never approved by the FDA due to unacceptable side effects. According to the investigators, Ig was "remarkably effective," during the early phase of infection (days 1-5) as demonstrated by the significant reduction in daily levels of virus in eye fluids compared to eye fluids obtained from control animals administered only saline.
Although this is the first study to ever demonstrate Ig's ability to block adenoviral-mediated eye infections, Dr. Gambotto is only slightly surprised by the results. "We use this compound in our laboratory on a regular basis to block the activity of the adenoviruses that we use in gene therapy experiments. So, we were pretty sure it would have some antiviral effects. We were not prepared, however, for it to be effective against so many strains and to demonstrate almost no toxicity," he explained.
Because conjunctivitis is so contagious, Dr. Gambotto and his investigators believe that topical Ig may be of value in many settings, including ophthalmology units in hospitals, pediatric units, community clinics and in global public health programs. Furthermore, due to its broad spectrum of antimicrobial properties, they believe that topical ocular application of Ig may be effective against other viral and bacterial causes of conjunctivitis.
This research was funded by the National Eye Institute, the Eye and Ear Foundation of Pittsburgh and the University of Pittsburgh Office of Technology Management. In addition to Dr. Gambotto, others involved in this study include Edward C. Nwanegbo, M.D., Eric G. Romanowski and Y. Gerold Gordon, M.D., of the University of Pittsburgh School of Medicine.