A common drug may help treat a rare genetic disorder

DENVER – A drug found in almost every medicine cabinet could be a treatment for a rare genetic disorder.

Ibuprofen can help children with mutations in a gene called MAN1B1suggests a study on fruit flies. Geneticist Clement Chow of the University of Utah in Salt Lake City reported the findings Nov. 6 at the annual meeting of the American Society of Human Genetics.

The MAN1B1 protein normally removes a sugar called mannose from misfolded proteins and specifically disposes of them. Children who inherit two defective copies of it MAN1B1 Genes have developmental delays, are prone to obesity and aggression, have distinctive facial features, and a host of other problems. There is currently no cure or treatment for the disease called MAN1B1 congenital glycosylation disorder.

Chow and colleagues decided to test a range of already approved drugs to see if any might help. This type of drug reuse research is widespread. The approach is “important because people with rare diseases can't just sit around and wait for a drug to be developed, which can take decades,” Chow said.

The team created fruit flies in which MAN1B1 had mutated in the eyes of the flies. The mutation causes the eyes to be small and rough. The researchers tested around 1,500 existing drugs in no time. Of these, 51 restored the flies' eyes to their usual large, ruby ​​red state and 47 made the condition worse. Of the medications that returned the eyes to normal, nine were nonsteroidal anti-inflammatory drugs, or NSAIDs, including ibuprofen and related painkillers.

These medications inhibit the action of the enzymes COX1 and COX2 to reduce inflammation in the body. In flies lacking MAN1B1, COX activity was high. Treatment with ibuprofen could lower it. And genetically lowering the amount of COX also restored normal eye shape, suggesting that the overzealous enzyme is a problem when MAN1B1 isn't around to perform a quality check.

Flies completely lacking MAN1B1 in their bodies also had persistent seizures when researchers slammed the vial containing the flies on the counter. But treating the flies with ibuprofen made the flies less susceptible to attacks.

The results of the fly experiments were so promising that a doctor treated three children with MAN1B1 mutations with low-dose ibuprofen. The results are preliminary, but “things are looking pretty positive,” Chow said.