A common drug may help treat a rare genetic disease

DENVER — A drug found in nearly every medicine cabinet could be a treatment for a rare genetic disease.

Ibuprofen can help children with mutations in a gene called MAN1B1suggests a study on fruit flies. Geneticists Clement Chow of the University of Utah in Salt Lake City reported the results 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, targeting them for destruction. Children who inherit two faulty copies of MAN1B1 they have developmental delays, are prone to obesity and aggression, have distinctive facial features and a host of other issues. There is currently no cure or treatment for the disease, called MAN1B1 congenital glycosylation disorder.

Chow and colleagues decided to test a battery of already approved drugs to see if any might help. This type of drug repurposing research has become commonplace. The approach is “important because people living with rare diseases can’t just sit around waiting for a drug to be developed, which can take decades,” Chow said.

The team made fruit flies in which MAN1B1 it was mutated in the eyes of flies. The mutation causes the eyes to be small and rough. The researchers tested about 1,500 existing drugs on flies. Of these, 51 returned the flies’ eyes to their usual large, ruby-red state, and 47 worsened the condition. Of the drugs that brought the eyes back to normal, nine were nonsteroidal anti-inflammatory drugs, or NSAIDs, including ibuprofen and related pain relievers.

These drugs inhibit the action of enzymes known as COX1 and COX2 to reduce inflammation in the body. In flies lacking MAN1B1, COX activity was high. Treatment with ibuprofen can lower it. And genetically knocking down the amount of COX also restored normal eye shape, indicating that excess enzyme is a problem when MAN1B1 isn’t around to perform a quality control on it.

Flies that completely lacked MAN1B1 in their bodies also had prolonged seizures when the researchers tapped the vial containing the flies on the counter. But treating the flies with ibuprofen made the flies less prone to seizures.

The results from the fly experiments were promising enough that a doctor started three children who had MAN1B1 mutations on low-dose ibuprofen. The results are preliminary, but “things look pretty positive,” Chow said.