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/

NSAIDs Active in Prevention of Colorectal Cancer

     A recent study at the University of Pittsburgh Cancer Institute has shown that non steroidal anti-inflammatory drugs, or NSAIDs, protect against the development of colorectal cancer. Although this has long been suggested, these scientists have finally discovered why. The NSAIDs, such as aspirin or ibuprofen, work by inducing cell suicide pathways in intestinal stem cells that carry a certain mutated and dysfunctional gene.

     The team researching this used animal models and examined tumor samples from patients who had and hadn't taken NSAIDs. Their results showed that the NSAIDs do in fact activate a cell-death pathway. Healthy cells lack the mutation, so the NSAIDs cause no harm to them. Their conclusion is that NSAIDs initiate the early destruction of cells that could be precancerous.
    The scientists plan to use their discovery to design new drugs that are more effective in cancer prevention for those high at risk of colon cancer. They say ideally they could harness the tumor-killing traits of NSAIDs and avoid the side effects such as ulcers and gastrointestinal bleeding.
    I found this article to be interesting because colon cancer is so prevalent and dangerous. Colorectal cancer is the third leading cause of cancer-related deaths in the country, and I personally know people who have been affected by it. NSAIDs seem like such a common drug, but clearly their effects are more complex than most people would think. The idea of using them to prevent cancer in this manner seems promising.

Article: http://www.sciencedaily.com/releases/2014/11/141103161950.htm