MELBOURNE, 27 October 2026 — Australian researchers have found a way to switch healthy but "sleeping" genes back on in Prader-Willi syndrome, a rare and complex genetic condition that affects about 400,000 people worldwide. The world-first study, announced on 27 October 2026, restored gene activity in patient-derived cells and animal models without causing problems elsewhere in the body — a safety result its authors describe as the critical step towards future treatments that target the cause of the condition rather than its symptoms.
The discovery centres on a protein called SMCHD1, first identified at Melbourne's Walter and Eliza Hall Institute (WEHI) in 2008. In Prader-Willi syndrome, SMCHD1 helps keep certain genes switched off — genes that are essential for development and brain function. Removing it, the researchers found, lifts that genetic "brake" and lets the dormant genes wake up.
Illustration: A DNA helix with a silent segment lighting up, representing dormant genes being switched back on.
What Happened
The study, titled "SMCHD1 is a target for gene-activation therapy to treat Prader-Willi syndrome," is published in the journal Science Advances (DOI: 10.1126/sciadv.aej5702). The WEHI team combined CRISPR gene-editing, stem-cell and genomic technologies to track what happened when SMCHD1 was removed, measuring the effects across thousands of genes and in the most disease-relevant brain tissue.
The headline result has two parts. First, gene activity could be restored: dormant genes switched back on in both patient-derived stem cells and animal models. Second, and just as importantly for any future medicine, that restoration happened without disrupting the rest of the body — a finding the researchers present as the strongest evidence so far that the approach can work safely in the models tested.
"We thought reactivating the 'sleeping' genes might be possible — what we didn't know was whether we could do it safely," said lead researcher Professor Marnie Blewitt, Deputy Director of WEHI and head of its epigenetics laboratory. "We now have the strongest evidence that removing SMCHD1 can restore gene activity lost in Prader-Willi syndrome without disrupting the rest of the body."
Therapeutic development is now advancing through Togglelux Therapeutics, a Melbourne-based biotechnology company and WEHI spinout focused on disease-modifying treatments for Prader-Willi syndrome. The study was supported by the Prader-Willi Research Foundation Australia and the Foundation for Prader-Willi Research USA, organisations founded and led by families affected by the condition, along with Australia's National Health and Medical Research Council and other funders.
Background
Prader-Willi syndrome is a complex condition that affects the brain and causes lifelong physical and developmental challenges. Its symptoms include developmental delays and intellectual disability, along with an insatiable appetite that can lead to obesity. WEHI's earlier explanation of the condition describes how SMCHD1 keeps some genes on one copy of chromosome 15 "asleep," preventing them from compensating for non-functional genes on the other copy.
For families, the daily reality is demanding. People with Prader-Willi syndrome often rely on multiple medications, surgeries and specialist care, but those treatments address symptoms rather than the underlying cause, providing limited relief. Professor Blewitt, who works closely with affected families, described children undergoing multiple surgeries for scoliosis and families whose lives revolve around medications, specialist appointments and managing often life-threatening symptoms.
"Prader-Willi is one of the most complex medical conditions a family can face," she said. "That's why the possibility of a treatment that targets the root cause, rather than symptoms, is so significant."
The new findings are the culmination of nearly two decades of research led by Blewitt, beginning with her team's discovery of SMCHD1 in 2008. "This is my life's work, so it's incredibly rewarding to finally see this approach succeed and bring hope to patients," she said. "Watching those dormant genes 'wake up' in both patient-derived stem cells and animal models was a powerful confirmation that the strategy works."
Kathlene Jones, chief executive of the Prader-Willi Research Foundation Australia, said the findings are an important step towards treatments that target the root cause. "Most people can't conceive what daily life is like for a person living with Prader-Willi syndrome," she said. "Our children and adults have to navigate a world full of food they can't eat, while feeling an intense drive to consume it. That relentless pressure can bring great distress and very challenging behaviours that affect the whole family. A treatment that addresses the root cause of the disease would be transformational."
Illustration: Researchers studying brain cell cultures in a laboratory, representing the study's work in disease-relevant brain tissue.
Why It Matters
The study matters first because of what it proves about safety. Many gene-targeting ideas fail not because the target is wrong but because switching a gene on or off has unwanted effects elsewhere in the body. Showing that SMCHD1 can be removed in laboratory models while restoring gene activity without throwing the wider body into disarray is what turns an interesting laboratory result into a credible starting point for drug development — particularly for babies and young children, who stand to gain most from early intervention.
Second, it reframes how a whole class of genetic conditions might be treated. Rather than replacing a faulty gene or managing each symptom separately, the gene-activation approach aims to wake up healthy copies of genes that are already present but silenced. If that strategy can be turned into a medicine, it could offer a template for other conditions where healthy genes are kept dormant by similar mechanisms — though researchers stress that each condition would need its own evidence.
Third, the story illustrates the role of small, family-led organisations in rare-disease research. Prader-Willi syndrome affects a relatively small number of people compared with common conditions, which can make commercial research investment harder to attract. Here, family-founded foundations helped fund the work from its early stages, and a local spinout company is now carrying it towards potential medicines — a path from public institute discovery to translation that rare-disease advocates often call for but rarely see completed.
What Happens Next
The researchers are clear about where this work stands: it is still at an early stage, and it is not a treatment. Turning a laboratory switch into a medicine means solving delivery, dosing and long-term safety, and each of those steps can take years. No one involved is presenting the findings as a ready therapy, and families should not expect a medicine imminently.
What comes next is therapeutic development through Togglelux Therapeutics, with the goal of producing potential new medicines that block SMCHD1 in a controlled, deliverable way. That work will need to show that the effect seen in cells and animal models can be reproduced safely in people, starting with the careful, staged trials that any new medicine must pass.
For the Prader-Willi community, the immediate value of the announcement is narrower but still significant: a validated target, evidence that the body can tolerate the change in the models tested, and a concrete development path where previously there was mainly hope. As Jones put it, while still at an early stage, the work is a testament to what can be achieved when scientists and small, family-led patient organisations collaborate. This article provides general information only and is not medical advice; families seeking guidance about Prader-Willi syndrome should speak with their own clinicians.
Illustration: A parent and child sharing a meal at home, representing daily life for families affected by Prader-Willi syndrome.
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FAQ
What is Prader-Willi syndrome?
It is a rare, complex genetic condition affecting about 400,000 people worldwide, causing developmental delays, intellectual disability and an insatiable appetite that can lead to obesity, among other challenges.
What did the WEHI researchers discover?
They found that removing a protein called SMCHD1 lifts a genetic "brake," allowing healthy but dormant genes to switch back on in patient-derived cells and animal models, without causing problems elsewhere in the body.
Where was the study published?
The study, "SMCHD1 is a target for gene-activation therapy to treat Prader-Willi syndrome," is published in Science Advances (DOI: 10.1126/sciadv.aej5702) and was announced on 27 October 2026.
Is this a treatment patients can use now?
No. The work is at an early, preclinical stage. Turning the discovery into a medicine requires solving delivery, dosing and long-term safety, and clinical trials would still be needed.
What happens next?
Therapeutic development is advancing through Togglelux Therapeutics, a WEHI spinout focused on disease-modifying treatments for Prader-Willi syndrome.
Sources
WEHI, "Switching on healthy silent genes reveals new way to treat rare genetic disorder," announced 27 October 2026 (via WEHI, Scimex and Medianet News Hub). Study: "SMCHD1 is a target for gene-activation therapy to treat Prader-Willi syndrome," Science Advances, DOI: 10.1126/sciadv.aej5702. Quotes from Professor Marnie Blewitt and Kathlene Jones as published by WEHI.
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