Hope for Treating MAN1B1 Mutation: How Ibuprofen May Help

  

                            

The MAN1B1 gene mutation, an autosomal recessive condition, disrupts a critical mechanism for identifying and removing misfolded proteins in the body. Children inheriting two copies of the mutated gene suffer developmental delays, obesity, aggression, seizures, and distinctive facial features. Currently, there is no cure or specific treatment for this rare disorder.   

Geneticist Clement Chow and his team sought to address this challenge by screening existing drugs for their potential to treat the condition. Using fruit flies engineered with the mutation—visible in their abnormally small, rough eyes—they tested around 1,500 drugs. Remarkably, 51 drugs restored the flies' eyes to a normal state, including nine NSAIDs such as Ibuprofen and Naproxen. 

NSAIDs work by inhibiting COX1 and COX2 enzymes, reducing inflammation. Interestingly, the MAN1B1 mutation appears to cause excessive COX enzyme activity, which NSAIDs can help regulate. In the fruit fly model, NSAIDs not only improved eye morphology but also reduced seizure activity—a promising result that led doctors to begin low-dose NSAID treatment in three affected children. 

This discovery underscores the value of repurposing approved drugs for rare genetic disorders. While further research is needed, these findings offer hope for families seeking relief from this challenging condition. 

References:

https://www.sciencenews.org/article/common-drug-treat-rare-genetic-disease

https://rarediseases.org/mondo-disease/man1b1-congenital-disorder-of-glycosylation/