UTHealth, PLx Pharma to test phosphatidylcholine-enriched version of indomethacin in PDA model

PLx Pharma Inc, a Houston-based pharmaceutical company developing a medical discovery made at The University of Texas Health Science Center at Houston (UTHealth) Medical School, has been awarded $565,449 for the first year of a potential two-year $1,118,398 grant to conduct research designed to enhance a treatment for premature babies with a common congenital heart defect.    

Patent ductus arteriosus (PDA) is a leading cause of death in low birth weight premature infants. It can occur when a heart vessel that normally closes on its own after birth remains open. It can affect about half of the very low birth weight infants. The grant is from the Eunice Kennedy Shriver National Institute of Child Health & Human Development.

A major breakthrough in the treatment for PDA occurred with the discovery that a non-steroidal anti-inflammatory drug (NSAID) named indomethacin speeds the closure process. It is the standard of care in many hospitals, often administered over a two- or three-day period and given intravenously to babies with PDA.

The discovery allowed doctors to give parents a less invasive and safer alternative to surgery for newborns with PDA.

However, this medical treatment is associated with some health risks. Indomethacin can be hard on the gastrointestinal tract (GI) of newborns, much like aspirin can damage the GI tracts of adults, said J. Marc Rhoads, M.D., who is advising the PLx Pharma team and is director of the Division of Gastroenterology and Nutrition in the Department of Pediatrics at the UTHealth Medical School.

"For example, about 3 percent of very low birth weight infants will develop spontaneous intestinal perforation, and the risk is approximately twofold greater if they have been treated with indomethacin. This is why it is important for physicians and parents to weigh the pros and cons of treatments," Rhoads said.

PLx Pharma and UTHealth are working to reduce the GI toxicity of NSAIDs by formulating this family of drugs with a natural lipid named phosphatidylcholine. The scientists believe this formulation could mitigate problems associated with indomethacin PDA treatment.

The plan is to test a phosphatidylcholine-enriched version of indomethacin in a preclinical model of PDA, according to Lenard Lichtenberger, Ph.D., and Elizabeth Dial, Ph.D., who are leading this study and are on the faculty of the Department of Integrative Biology and Pharmacology at the UTHealth Medical School.

"This product is being developed to meet a serious unmet need for this compelling patient population," said Ron Zimmerman, president of PLx Pharma.

Lichtenberger pioneered the use of phosphatidylcholine as a way to make NSAIDs safer for the millions in the United States who count on this family of drugs for pain relief and to protect against heart disease. Clinical trials using aspirin and ibuprofen formulated with this technology have been successful and suggest a 70 percent reduction in the risk of upper GI ulcers.