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A team of researchers at Children’s Hospital of Pittsburgh of UPMC has been able to identify a molecular switch that, it is blocked from working, it might be of some help in reversing necrotizing enterocolitis (NEC)m which is one of the leading causes of death in premature babies.

Necrotizing enterocolitis is a very sever inflammatory disease that occurs in the intestines of about 5% of all premature babies. Figures show that necrotizing enterocolitis can be fatal in as many as 50% of the cases. In the most extreme of the cases, necrotizing enterocolitis can lead to perforation of the intestine and if this is not treated immediately by emergency surgery, it can be fatal.

The number of cases of necrotizing enterocolitis is rising due to the fact that more premature infants are being saved.

The researchers worked in the lab and used an animal model of necrotizing enterocolitis. The team found that when they successfully blocked a molecular receptor that is known as Toll-like receptor-4 (TLR4), the damaged tissue in the intestine that is the result of necrotizing enterocolitis was repaired.

It is the responsibility of this Toll-like receptor to act as a defense mechanism and switch on the immune response in the intestine. However, in the case of some of the premature infants who experience stress such as oxygen deprivation and have toxins caused by underdeveloped lungs there is an overproduction of TLR4. Unless they are able to find a way to stop the overproduction, it can lead to cell death as well as prevent enterocytes from moving to the site of the wound in the intestine and closing it up.

When they interfered with the production of another molecule that is also associated with TLR4 – focal adhesion kinase (FAK)- they were able to shut down the overproduction of the TLR4 in intestinal cells.

When the overproduction of the TLR4 stopped, the enterocytes were again able to travel to the intestines and once there, they repaired the damage that was done to the intestinal tissue. The team is continuing with the research into the development of future treatments that will be able to block the overproduction of the TLR4 by regulating its interactions with the focal adhesion kinase. They are looking at the possibility that they may be able to administer the treatments as part of the oral feeds for the infants.

The lead researcher on the project is David J. Hackam, MD, PhD, a pediatric surgeon and scientist at Children’s Hospital.