Synthetic Peptides May Prevent Some Fas Injury: Small Amounts of These Compounds Might Avert Brain Damage Caused by Fetal Alcohol Syndrome

Article excerpt

NEW ORLEANS -- In a mouse model of fetal alcohol syndrome, two synthetic peptides have been shown to prevent learning problems in young adults who were prenatally exposed to alcohol.

The findings of this research are far from clinical application, but they demonstrate an exciting potential for averting damage because of maternal alcohol intake, Dr. Catherine Spong said at the annual meeting of the Society for Maternal-Fetal Medicine.

"We already know that women should not drink during pregnancy, and we counsel them to stop," said Dr. Spong, chief of the pregnancy and perinatology branch of the National Institute of Child Health and Human Development. "But most often, women won't admit to drinking during pregnancy, so a prenatal intervention might be difficult. We wanted to know if you could treat after delivery and prevent or reverse damage."

Although Dr. Spong has not positively identified the mechanism by which the learning disabilities improve, her results suggest that at least some types of brain damage associated with prenatal alcohol exposure can be reversed. Other researchers are also investigating the peptides' effects on damaged brain cells: The National Institute on Aging is using NAP and SAL in an Alzheimer's model, and Dr. Spong will soon begin to look at how they perform in a model of cerebral palsy.

The compounds used in this research are d-NAPVSIPQ (NAP) and d-SALLRSIPA (SAL). Those synthetic peptides mimic the fetal neuroprotective and growth-promoting properties of novel proteins that are regulated by vasoactive intestinal peptide (VIP). VIP is thought to protect against oxidative injury and reduce neuronal apoptosis during embryogenesis. Alcohol blocks those messages, and researchers believe that message disruption is one factor in fetal alcohol syndrome.

They theorize that administering small amounts of the highly active synthetic peptides might prevent some of the alcohol-induced fetal injury.

In 2001, Dr. Spong published research showing that NAP and SAL prevented fetal growth restriction and microencephaly in a mouse model of fetal alcohol syndrome (J. Pharmacol. Exp. Ther. 297[2]:774-79, 2001). In that study, Dr. Spong treated pregnant mice with the peptides before or after alcohol injection. The injections were carried out on day 8 of pregnancy, as mouse fetuses are highly susceptible to cellular disruption on that day, leading to a very stringent test for the peptides. The model simulates binge drinking in human pregnancy.

Fetal brain and body weights were obtained on pregnancy day 18. In mice treated with alcohol alone, 36% of the fetuses had miscarried, compared with 4% of the untreated controls. In mice pretreated with NAP or both peptides, the death rate dropped back to the control level. Alcohol alone caused a reduction of brain and body weight in the surviving fetuses but again, the NAP-SAL combination brought them back to control levels.

Her most recent research shows that the peptides are also beneficial when administered postnatally. Following the same fetal alcohol syndrome model, Dr. Spong injected 12 pregnant mice with alcohol and 8 with placebo on gestational day 8. The pups were then delivered and allowed to grow normally to young adulthood.

For the learning experiment, Dr. Spong used all male offspring. Using males eliminated the possibility of performance variability because of hormonal cycling in females. …