Among medical mysteries, this could be the toughest: Why, when the human body's immune system is designed to protect it from bacteria, viruses and disease, would its soldier antibodies mistakenly and at random attack healthy tissue?
Scientists at the Eccles Institute of Human Genetics at the University of Utah reported Thursday they have found at least a partial answer in two unrelated neurological disorders.They have identified unusual antibodies that interact with a specific protein in the brain and cause an overactive immune system, where antibodies act as toxic drugs.
Writing for the scientific journals Neuron and Molecular Medicine, researchers Lorise Gahring, Scott Rogers and Dr. Roy Twyman say the antibody discovery not only sheds new light on how epilepsy occurs and how cancer sometimes causes severe neurological syndromes, it suggests that such diseases can be treated with agents that suppress the immune function.
The research already has restored life to normal for a few children long plagued by seizures brought by Rasmussen's encephalitis, the rare form of epilepsy identified in the research. Between 30 and 40 children nationally have this type of epilepsy, which is not diagnosed in adults.
The findings also offer hope for cancer victims, primarily women who've battled breast, ovarian or lung cancer. The scientists report that the antibodies that attack glutamate receptors in about 14 percent of cancer patients can ultimately result in impairment of learning, loss of memory and the inability to walk. The problems can persist and can be permanent, even when the cancer is treated successfully.
The glutamate receptor is one of the most important proteins in the brain, playing a role in learning and memory, seizures, strokes and possibly other degenerative diseases such as Alzheimer's and Lou Gehrig's disease.
The research and its treatments may have far-reaching implications as diagnoses for patients with neurological problems are re-evaluated, Gahring said.
For example, in order to diagnose Rasmussen's enchephalitis, the child must undergo a brain biopsy. "This is a frightening procedure for parents and many don't do it," she said. "There may also be older patients who this will apply to. There's a possiblity that this is a highly underdiagnosed disease."
The normal job of antibodies is to bind to receptors in the brain and turn them on to enhance their normal function, the scientists say. That can become a serious problem because over-excitation of a nerve cell can cause epileptic seizures and progressive brain destruction.
"Our discovery that the immune system produces antibodies that can target and kill unique brain cells allows doctors to treat some of these diseases by controlling the abnormal immune response," Rogers said.
Dr. Kevin Staley, a pediatric neurologist at the Children's Hospital in Denver, has used the treatment to successfully treat a Wyoming girl, who may have to take them the rest of her life.
"Are the antibodies a perfect treatment? Probably not, but this greatly improves life for these young people," he said.
"This isn't going to stop Rasmussen's enchephalitis, but it points out a whole new way to deal with the disease," Staley said.
Diseases and disorders that attack the brain remain frightening to observe and difficult to regulate through medication and treatment, said Twyman.
"There are many things we can't explain. In many cases, we have to put people to bed and make them as comfortable as we can," he said. "But at least with these horrible diseases, we can offer a treatment and we can offer a diagnosis early."