Drug to prevent deadly immune response on the anvil

WASHINGTON - Researchers, led by an Indian origin scientist, have isolated a molecule, small enough to be used as a drug, that can shut down a dysfunctional immune response that causes deadly hemorrhagic shock, results in delayed death of heart attack patients, promotes rejection of transplanted organs and destroys joints in patients with rheumatoid arthritis, according to a study.

The molecule, a modified peptide, was extracted from the relatively huge protein shell of a common virus that is a frequent cause of childhood diarrhea, according to the research conducted by a team at Eastern Virginia Medical School and Children’s Hospital of The King’s Daughters.

The discovery marks a quantum leap toward clinical application by creating a powerful effect with a molecule small enough to be used in medications.

“This puts us in a position to move rapidly from in-vitro testing to in-vivo testing,” says Neel Krishna, PhD, an assistant professor of microbiology and molecular cell biology at EVMS and a pediatric virologist at CHKD.

Five years back, the researchers inserted a shell of a virus that causes childhood diarrhea into a Petri dish primed to measure the response of a primordial component of the human immune response known as the complement system.

The complement reaction completely stopped.

“Being able to pharmacologically modulate the complement system could have a huge impact on the practice of medicine, potentially saving the lives of victims of hemorrhagic shock, heart attack patients, and even infants who have suffered prolonged hypoxia. It could also have a significant impact on treating a wide range of autoimmune and inflammatory diseases,” said Krishna.

In earlier research, the authors showed that the introduction of the harmless protein shell that encases the astrovirus, which causes pediatric diarrhea, shuts down two of the three methods used by the complement system to destroy damaged cells, but doesn’t interfere with the part of complement reaction that can offer protection from invading pathogens.

The molecule that modulated the complement cascade, however, was relatively large, consisting of 787 amino acids, too sizable to be used therapeutically.

By meticulously testing smaller shards of the shell, researchers found and then modified a shard consisting of just 30 amino acids that actually was more effective than the larger molecule.

That smaller segment, a modified peptide dubbed E23A, makes it a viable candidate for in-vitro testing of the compound.

“In-vitro testing is a significant step toward developing a drug that can be used therapeutically,” said Krishna.

The study has been published in Molecular Immunology. (ANI)