University of Pennsylvania researchers have earned acclaim in recent years for using a type of genetic engineering to treat leukemia.
Now another Penn team says the tactic may be effective against a debilitating skin disease.
That is because the two maladies have something in common: deviant cells of the immune system.
The treatment for the skin disease, a rare autoimmune disorder called pemphigus vulgaris, has been demonstrated so far only in mice, the scientists reported online Thursday in the journal Science.
But because the related leukemia treatment has achieved dramatic results in people, the authors are optimistic that they may someday be able to treat - and even cure - pemphigus in humans, along with certain other diseases in the autoimmune family.
Scientists tend to shy away from the word cure, but a cure is possible with this treatment "if we can figure out how to use it properly," said Penn's Aimee S. Payne, one of the study's senior authors.
Another autoimmune disease that might yield to similar treatment is the neuromuscular condition myasthenia gravis, said Payne, an associate professor of dermatology at Penn's Perelman School of Medicine. Conditions such as lupus and multiple sclerosis, however, are more complicated and would need a different approach, she said.
Autoimmune diseases occur when the immune system mistakenly perceives the patient's own tissue to be foreign and, as a result, attacks it.
In the case of pemphigus, the attack is directed at a type of protein that helps skin cells stick together. When rogue immune cells seek out this protein, the skin deteriorates and blisters, especially inside the mouth and throat. Eating and drinking become increasingly difficult, even excruciating, and patients can suffer infections.
The rare condition was often fatal until the advent of cortisone and other immune-suppressing steroids in the mid-20th century. Physicians also prescribe nonsteroidal immune suppressants.
But both of those drug classes have complications, and because they suppress the immune response, patients remain prone to infection.
"When you have breakdown of your skin, and then you take away their immune system, you've put them at high risk of infection," said Penn's Michael C. Milone, the co-senior author of the new study.
So for years, the goal has been to somehow target only those immune cells that had gone rogue, leaving the rest intact.
Milone, a former member of the Penn lab that developed the successful treatment for certain leukemias, started discussing the problem with Payne three years ago. The idea came from her postdoctoral researcher Christoph T. Ellebrecht.
Both the leukemias and the blistering disease are marked by abnormalities in a staple of the immune system called a B cell. In certain leukemias, the B cells become malignant, whereas in the blistering disease, B cells mistakenly attack the protein that holds skin together.
Working with Penn professor Carl H. June, Milone helped to "engineer" another type of immune-system soldier called T cells, training them to destroy B cells. But that approach wipes out all B cells, malignant and healthy, so patients have to take immune-boosting drugs for the rest of their lives.
To treat the blistering disease, Milone and Payne wanted a targeted approach, tweaking T cells so that they would destroy only the rogue B cells.
They did so by turning the T cells into a kind of bait, attaching to them a portion of the DNA recipe for the skin protein. In theory, the malfunctioning B cells would be drawn to these baited T cells, which would then destroy them.
The bait DNA was inserted in the T cells by means of a virus that was customized so it could not replicate and cause disease.
Mice do not naturally get the blistering disease. So the scientists induced it by injecting a dozen of the animals with rogue B cells, then administered the baited T cells to half of them.
Sure enough, after a couple of weeks, the treated mice had no blisters in their mouths, whereas five of the untreated animals did. Tests also revealed that levels of the rogue B cells had declined sharply in the treated mice but not in the untreated group.
What's more, the treatment did not appear to affect other tissues in the body - always an area for concern when scientists interfere with the immune system.
Other scientists who were not involved with the study said the results were promising.
Betty Diamond, an autoimmune-disease researcher at the Feinstein Institute for Medical Research in Manhasset, N.Y., cautioned that the mouse "model" of the disease was artificial and would not necessarily translate to humans.
"This is very exciting," she said. "But this is going to require a thoughtful and cautious progression to the clinic."
The apparent success of Penn's targeted approach prompted Whitney A. High, associate professor of dermatology and pathology at the University of Colorado School of Medicine, to make a military analogy.
"They're saying, 'What if we knew what the hostiles were, and we sent in a field team to take out just those hostiles?' " said High, who treats patients with the blistering disease.
Milone said a good deal of the team's success was driven by Ellebrecht, the first author of the study.
Next on the team's agenda is to try treating the blistering disease in dogs, which get it naturally. The scientists also are discussing how to proceed with trials in humans.
They say they will not have to worry about one problem that arose with the cancer treatments.
In some leukemia patients, the T cells become ineffective because the malignant B cells mutate.
But in the skin disease, if the rogue B cells were to mutate so that they were no longer drawn to the baited T cells, then they would, by definition, no longer be drawn to the skin protein either, Payne said. The disease would go away.
"It literally can't escape," she said.