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Rabies treatment team urges veterinary schools to scientifically define the Milwaukee protocol

March 27, 2007

The appeal, by Rodney Willoughby, M.D., associate professor of pediatrics, appears in the April 2007 issue of Scientific American. In it he chronicles the scientific rationale behind the survival of a 15-year-old Wisconsin girl, Jeanna Giese, in 2004 and the six subsequent attempts made elsewhere to replicate the treatment, now dubbed the Milwaukee protocol.

"Our novel treatment has stirred controversy among medical specialists; some claim that Jeanna's cure was a fluke," says Dr. Willoughby. "Although the few attempts to replicate the treatment have not saved the lives of any other rabies patients, I fervently hope that we are on the right track. At the very least, researchers should initiate animal studies that parallel treatments in humans to determine which of the elements in our protocol can help defeat rabies."

Promising new research by Dr. Willoughby and faculty colleague Jeanette Vasquez-Vivar, Ph.D., along with Atlanta researchers, Dr. Keith Hyland at Horizon Molecular Medicine and Dr. Charles Rupprecht at the Centers for Disease Control and Prevention, offers new hope for a cure of this heretofore 100 percent fatal disease.

The researchers have discovered a deficiency of a vitamin-like molecule in rabies patients. The molecule, biopterin, can be supplemented and promises to make rabies even more treatable than it was when Jeanna survived.

According to Dr. Willoughby, of the six attempts by others to replicate the treatment, only two closely followed the protocol, and these two children survived twice as long as the average for rabies patients in the U.S. Although they ultimately died from complications of the disease or their care, both were clearing rabies virus from their bodies when they died.

"The sense is that we're very close to a second survivor," he says. "What is needed most is an animal model of rabies. Meanwhile, treatment of human rabies in medical intensive care units continues haphazardly, without scientific input."

Vaccines against the rabies virus can prevent development of the illness after a bite by an infected animal. But, until recently, doctors could hold out no hope for patients who failed to get immunized soon after being bitten. Once the symptoms of rabies appeared -normally within two months of the bite- death was inevitable, in a week or less.

Having pushed survival with human rabies from one week (untreated) to almost four weeks with the Milwaukee protocol, virtually nothing is known about how the body responds that far out. The problem, according to Dr. Willoughby, is that animal studies will also require intensive care of animals for a week or more. The researchers hope to find these answers by treating rabid animals in veterinary intensive care units.

Rabies is one of the oldest and most feared diseases. It attacks the brain, causing agitation, terror and convulsions. Victims suffer painful throat spasms when they try to drink or eat. Paralysis follows, yet people infected with rabies are intermittently alert until near death and can communicate their fear and suffering to family and caregivers.

Medical College of Wisconsin