Therapeutics: Serotonin (5-HT4) receptor; serotonin (5-HT) transporter (SLC6A4; SERT)
Mouse studies suggest 5-HT4 receptor agonists could help treat constipation in autism patients harboring the G56A mutation in SLC6A4. Mice systemically expressing the autism-associated G56A SLC6A4 mutation had fewer total enteric neurons and fewer serotonergic neurons in the gut, lower colorectal motility and peristaltic reflexes and longer GI transit times than wild-type mice. In the pregnant mouse dams carrying and then nursing offspring expressing the SLC6A4 mutant, the 5-HT4 receptor agonist Resolor prucalopride increased the total number of enteric neurons, colorectal motility and peristaltic reflexes and decreased GI transit time in the offspring compared with vehicle. Next steps include testing 5-HT4 receptor agonists in adult mice that have developed SLC6A4 G56A mutant-associated constipation and other enteric defects...