Scientists from Duke Health have found a molecule that might be an effective treatment option for a genetic disorder called Prader-Willi syndrome. The findings may also help researchers develop medications for treating other genetic disorders. The details are in a paper that was just published in the journal Nature Medicine.
Prader-Willi syndrome is a very rare disorder that occurs when a father passes down a copy of chromosome 15 with missing genes. The disorder causes developmental problems early on, leading to behavioral problems and learning disabilities later in life. Patients with Prader-Willi syndrome have hormone imbalances that often cause a feeling of constant hunger. Obesity is common and patients must have their diets restricted. While hormone therapy can help relieve specific symptoms, there is no cure for Prader-Willi syndrome.
A team of researchers began screening chemical compounds in an effort to find one that could activate the maternal copy of the problem gene. This would make up for the loss of the paternal copy, preventing symptoms of the disorder. The researchers used fluorescent markers in the embryonic cells of mice; the cells would light up if the gene was switched on. The team screened over 9,000 small molecules.
The researchers found that G9a inhibitors, a class of small molecules, activated the maternal copy of the missing gene. They tested the molecules on human cells and live mice with Prader-Willi syndrome. In both cases, the molecules worked as a fix for the genetic disorder. Live mice that were treated as newborns lived longer and had fewer Prader-Willi symptoms. G9a inhibitors appear to be good candidates for the development of proper treatments for Prader-Willi syndrome.
G9a inhibitors may be able to treat Prader-Willi syndrome and other disorders caused by silenced or deleted genes. Further research is needed before human trials can begin but the study represents a huge step in learning to treat rare genetic disorders.
Kim et al. Targeting the histone methyltransferase G9a activates imprinted genes and improves survival of a mouse model of Prader–Willi syndrome. Nature Medicine (2016).