Researchers at Melbourne's WEHI have shown that removing a protein called SMCHD1 lifts the genetic brake silencing healthy genes in Prader-Willi syndrome, restoring gene activity in patient-derived cells and animal models and opening a potential path to a treatment targeting the condition's cause.
Researchers at WEHI in Melbourne have discovered a way to release a genetic brake that silences healthy genes in Prader-Willi syndrome, opening a potential new path to treating the condition. The team showed that removing a protein called SMCHD1 lifts the brake, allowing healthy but dormant genes to switch back on.
About 400,000 people worldwide live with Prader-Willi syndrome, a complex condition that affects the brain and causes lifelong physical and developmental challenges. The disorder stems from a failure to express critical genes on the paternal copy of chromosome 15, while the maternal copies of those genes remain intact but are switched off by SMCHD1, an epigenetic regulator.
In the new study, researchers restored gene activity in patient-derived cells and animal models by removing SMCHD1, without causing problems elsewhere in the body, according to WEHI's announcement. Earlier WEHI work had shown that deleting SMCHD1 in mouse neural stem cells reactivated the maternal Prader-Willi genes without affecting other SMCHD1 targets, and the new findings extend that result toward a therapeutic approach.
The findings come from WEHI's own announcement, distributed through SciMex and the institute's news hub, and they are preclinical: the evidence so far is from patient-derived cells and animal models, not human trials, and the announcement names no journal publication. The discovery is being advanced toward potential new medicines through WEHI spinout company Togglelux Therapeutics, with medicinal chemistry work already under way on candidate compounds.
No treatment targeting the genetic cause of Prader-Willi syndrome is currently available; existing treatments address individual symptoms. A treatment that wakes the silenced maternal genes would aim at the cause rather than the symptoms, which is why the institute describes the result as world-first.
The next steps are drug development, not clinical use. The team must turn SMCHD1-blocking compounds into a safe clinical candidate and then test it in people, so any treatment remains years away even if the approach holds up.