A recent study suggests that ibuprofen, a common household drug found in almost every medicine cabinet, may be a potential treatment for a rare genetic disease known as MAN1B1-congenital disorder of glycosylation. This condition is caused by mutations in a gene called MAN1B1, which is responsible for removing a sugar called mannose off misfolded proteins and targeting them for disposal. Children with two faulty copies of this gene experience developmental delays, obesity, aggression, distinctive facial features, and other health issues. Currently, there is no cure or treatment available for this disease.
Geneticist Clement Chow and his team at the University of Utah decided to test a variety of already approved drugs to see if any might help with the MAN1B1 genetic disorder. This type of research, known as drug repurposing, has become increasingly common as it allows for potential treatments to be identified more rapidly than developing new drugs from scratch. For individuals living with rare diseases, waiting for the development of new treatments could take decades, so repurposing existing drugs offers a more immediate solution.
The team conducted experiments using fruit flies in which the MAN1B1 gene was mutated, causing the flies’ eyes to be small and rough. They tested approximately 1,500 existing drugs on the flies and found that 51 drugs restored the flies’ eyes to their normal state, while 47 made the condition worse. Among the drugs that improved the eye shape were nine nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen. NSAIDs work by inhibiting the action of enzymes known as COX1 and COX2, which are involved in reducing inflammation in the body.
In flies without MAN1B1, COX enzyme activity was high, leading to abnormal eye development. Treating the flies with ibuprofen or genetically lowering the amount of COX enzyme restored the normal eye shape, suggesting that the overactivity of this enzyme is problematic when the MAN1B1 gene is not functioning correctly. Flies lacking MAN1B1 also experienced prolonged seizures, however, treatment with ibuprofen reduced their susceptibility to seizures, indicating a potential therapeutic benefit of the drug.
Preliminary results from the fly experiments prompted a doctor to start three children with MAN1B1 mutations on a low-dose ibuprofen regimen. While the results are still in the early stages, Chow mentioned that the outcomes are looking positive. The use of ibuprofen to potentially treat this rare genetic disorder offers hope for affected individuals and their families, as there is currently no approved treatment available. Further research and clinical trials will be needed to confirm the effectiveness and safety of ibuprofen for individuals with MAN1B1-congenital disorder of glycosylation.
