Featured Research

from universities, journals, and other organizations

Researchers closer to development of drug to prevent deadly immune response

Date:
August 27, 2010
Source:
Eastern Virginia Medical School
Summary:
Researchers have isolated a molecule, small enough to be used as a drug, that can shut down a dysfunctional -- and at times, deadly -- immune response known as the complement system.

Researchers 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 paper published in Molecular Immunology.

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.

The publication comes almost five years after Dr. Krishna and Kenji Cunnion, MD, an associate professor of pediatrics at EVMS and an infectious disease specialist with Children's Specialty Group at CHKD, 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," says Dr. Krishna. "It could also have a significant impact on treating a wide range of autoimmune and inflammatory diseases."

The complement system is one of the oldest surviving remnants of the earliest life forms and exists in almost identical from in everything from seagulls to starfish.

It developed during millions of years in which the deadliest threat to all life forms, including humans, was not car accidents, heart attacks or the rejection of transplanted organs but infectious disease.

A complex cascade of dozens of biochemical reactions is designed to launch an attack that destroys the membranes of cells damaged by infection.

After trauma has left cells without oxygen for too long, the complement system kicks in when oxygen returns and lays waste to damaged cells that might otherwise survive. This is known as a reperfusion injury, and in some case occurs over a series of days.

In heart attacks, the death of heart cells during reperfusion can be irreversible and lethal. Multiple organ dysfunction syndrome caused by reperfusion injury is the leading cause of death in surgical patients and in trauma patients who survive the first 24 hours.

The inflammatory response also plays a major role in autoimmune and inflammatory diseases such as rheumatoid arthritis.

In earlier published 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," says Dr. Krishna.


Story Source:

The above story is based on materials provided by Eastern Virginia Medical School. Note: Materials may be edited for content and length.


Journal Reference:

  1. Jenny Q. Gronemus, Pamela S. Hair, Katrina B. Crawford, Julius O. Nyalwidhe, Kenji M. Cunnion, Neel K. Krishna. Potent inhibition of the classical pathway of complement by a novel C1q-binding peptide derived from the human astrovirus coat protein. Molecular Immunology, 2010; DOI: 10.1016/j.molimm.2010.07.012

Cite This Page:

Eastern Virginia Medical School. "Researchers closer to development of drug to prevent deadly immune response." ScienceDaily. ScienceDaily, 27 August 2010. <www.sciencedaily.com/releases/2010/08/100826182508.htm>.
Eastern Virginia Medical School. (2010, August 27). Researchers closer to development of drug to prevent deadly immune response. ScienceDaily. Retrieved August 27, 2014 from www.sciencedaily.com/releases/2010/08/100826182508.htm
Eastern Virginia Medical School. "Researchers closer to development of drug to prevent deadly immune response." ScienceDaily. www.sciencedaily.com/releases/2010/08/100826182508.htm (accessed August 27, 2014).

Share This




More Health & Medicine News

Wednesday, August 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Predicting Heart Transplant Rejection With a Blood Test

Predicting Heart Transplant Rejection With a Blood Test

Ivanhoe (Aug. 27, 2014) Now a new approach to rejection of donor organs could change the way doctors predict transplant rejection…without expensive, invasive procedures. Video provided by Ivanhoe
Powered by NewsLook.com
Better Braces That Vibrate

Better Braces That Vibrate

Ivanhoe (Aug. 27, 2014) The length of time you have to keep your braces on could be cut in half thanks to a new device that speeds up the process. Video provided by Ivanhoe
Powered by NewsLook.com
Smartphone App Tracks Your Heart Rate

Smartphone App Tracks Your Heart Rate

Ivanhoe (Aug. 27, 2014) A new app that can track your heart rate 24/7 is available for download in your app store and its convenience could save your life. Video provided by Ivanhoe
Powered by NewsLook.com
Stroke in Young Adults

Stroke in Young Adults

Ivanhoe (Aug. 27, 2014) A stroke can happen at any time and affect anyone regardless of age. This mother chose to give her son independence and continue to live a normal life after he had a stroke at 18 years old. Video provided by Ivanhoe
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins