By Huntly Collins
INQUIRER STAFF WRITER
Tens of thousands of Americans who suffer from various autoimmune disorders or who need organ transplants stand to benefit from a seven-year, $144 million federal research initiative announced yesterday.
The initiative, to be carried out by a consortium of nearly 40 medical centers, including the University of Pennsylvania Health Systems, will test a promising new way to turn off the immune response involved in the body's rejection of organ transplants and a host of diseases ranging from juvenile diabetes to multiple sclerosis.
Currently, for instance, people undergoing an organ transplant must take powerful, immunosuppressive drugs to prevent their body's immune system from rejecting the transplanted organ. But by suppressing the body's natural defenses, the drugs leave a person vulnerable to infections and cancer.
Under the approach to be tested as part of the new federal initiative, such immunosuppressive drugs would not be necessary. Instead, genetically engineered antibodies or other human proteins would be used to block one of several newly discovered molecular signals that are needed for the body to mount a full immune response.
The hope is that the new therapy - called immune tolerance - would turn off only the troublesome part of the immune response, leaving a person with enough natural defenses to fight infectious disease.
"With the traditional approach, you are trying to shoot a fly with an elephant gun," said Laurence A. Turka, an immunologist and kidney expert at Penn. "You can probably get the fly, but you can do a lot of damage, as well. The idea here is to develop a flyswatter."
Turka, who will be the principal investigator for the project at Penn, said he had used the approach to prevent rejection of heart and islet (a type of insulin-producing tissue) transplants in mice and to significantly reduce symptoms in the mouse version of multiple sclerosis. He said it was too soon to say when human trials might begin at Penn and exactly what diseases would be targeted.
Federal officials said the first human trials would involve islet transplants to cure juvenile diabetes, and kidney transplants. If the approach pans out for people undergoing such organ transplants, then it would be tried for those with autoimmune disorders, officials said.
Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), said the new initiative would put "the best of the best" scientists to work on "some of the most debilitating and chronic" immune-system diseases for which there are no effective therapies.
The seven-year research and clinical trial program - which involves the largest single contract ever let by the NIAID - is also sponsored by the Juvenile Diabetes Foundation and the National Institute of Diabetes and Digestive and Kidney Diseases. It will be coordinated by researchers at the University of Chicago and the University of Minnesota, leaders in islet transplants to treat juvenile diabetes.
Fauci said he expected that it would be two or three years before large-scale clinical trials were up and running at the various medical centers, including Penn.
The new approach is an outgrowth of fundamental breakthroughs, made over the last decade, in understanding how the immune system works.
Scientists have known for years that it was the white blood cells known as T cells that orchestrate the immune system's response to foreign invaders such as viruses and, mistakenly, to transplanted organs.
But over the last decade, scientists have discovered that while a foreign
invader may turn on the T cells, other immune-system molecules are needed
to direct the T cells to swing into combat against the invader. It is these
molecules that are to be selectively targeted in the new therapeutic approach.