Some conditions are less a matter of illness than of a stubborn silence written into the body's own instructions. For the roughly 400,000 people living with Prader-Willi syndrome, that silence shows up as a hunger that never rests, alongside developmental and intellectual challenges that shape a whole family's life. Researchers at the Walter and Eliza Hall Institute in Melbourne have now shown, in patient-derived cells and animal models, that lifting a single gene-regulating brake called SMCHD1 can wake genes that had been quietly dormant. The finding, published in Science Advances, is still e
Australian Researchers Reactivate Silenced Genes in Prader-Willi Syndrome, Targeting Root Cause
Children and adults with Prader-Willi syndrome face lifelong distress, multiple surgeries, dependence on medications, and often life-threatening symptoms, affecting whole families.
A brake on the genes, released in patient cells and animal models
Mark
Why does this one stand out from other Prader-Willi research?
Mimi
Because current care manages symptoms. This work goes after the silenced genes themselves, using a protein, SMCHD1, that acts as a brake on them.
Mark
And removing that protein turns the genes back on?
Mimi
In patient-derived cells and in animal models, yes. The team measured effects across thousands of genes and in the most disease-relevant brain tissue.
Luke
Worth being clear about where that evidence sits. These are cells and animals. No person has been treated, and the report doesn't describe any human trial.
Mark
Blewitt says safety was the key question. What did she actually claim?
Mimi
That this is the strongest evidence yet that removing SMCHD1 restores gene activity without disrupting the rest of the body.
Luke
That's her assessment, and "strongest evidence yet" is not the same as proven safe in children. The article gives no detail on long-term effects, and the world-first label comes from WEHI itself.
Mark
What role did families play?
Mimi
Two family-founded groups, the Australian and US Prader-Willi research foundations, supported the study. Jones called it a testament to small patient organisations working with scientists.
Luke
And the timeline is unknown. Togglelux is developing potential medicines, but nothing here says when, or whether, one reaches a clinic.
Il Polso
- A hunger that never lets up leaves people with Prader-Willi syndrome and their families under relentless, exhausting pressure.
- Current treatments only manage symptoms, leaving multiple surgeries, daily medications and life-threatening episodes as the lifelong norm.
- Researchers at WEHI removed the SMCHD1 brake using CRISPR and stem-cell methods, and the silenced genes switched back on in lab cells and animals.
- The approach is still at an early stage, and the spinout Togglelux Therapeutics is now working to turn it into medicines.
- The decisive test ahead is whether this can be done safely in babies and young children, the very patients who would need it most.
Some conditions are less a matter of illness than of a stubborn silence written into the body's own instructions. For the roughly 400,000 people living with Prader-Willi syndrome, that silence shows up as a hunger that never rests, alongside developmental and intellectual challenges that shape a whole family's life. Researchers at the Walter and Eliza Hall Institute in Melbourne have now shown, in patient-derived cells and animal models, that lifting a single gene-regulating brake called SMCHD1 can wake genes that had been quietly dormant. The finding, published in Science Advances, is still early, but it hints at a future in which medicine addresses the cause of a condition rather than only tending its symptoms.
For people living with Prader-Willi syndrome, food is everywhere and it is never safe to eat without limit. The drive to eat is relentless, and it brings great distress, very challenging behaviours and strain that reaches the whole family, as Kathlene Jones, chief executive of the Prader-Willi Research Foundation Australia, describes it.
At the Walter and Eliza Hall Institute of Medical Research in Melbourne, scientists have reported a way to switch back on healthy genes that are silenced in the condition. The condition affects about 400,000 people worldwide, touching the brain and bringing lifelong developmental delay, intellectual disability and obesity. Most people depend on a mix of medications, surgeries and specialist care that eases symptoms but cannot touch the cause.
The study focuses on SMCHD1, a protein the institute discovered in 2008, which acts as a genetic brake keeping important genes switched off. Using CRISPR editing and stem-cell methods, the team removed it and watched thousands of genes respond. In patient-derived cells and animal models, the brake released and the dormant genes returned. Professor Marnie Blewitt, who led the work, says safety was always the central question, since any treatment would be given to babies and young children. For her, the result caps nearly two decades of work, and she has met the families whose days revolve around symptoms.
Families helped make this possible, through foundations in Australia and the United States that were founded and led by people affected by the condition. Jones called the findings an important step and said a root-cause treatment would be transformational, while stressing that the work is early. The next stage is already underway at Togglelux Therapeutics, a WEHI spinout developing potential medicines, and what will matter most is whether the safety seen in cells and animals holds for the youngest patients.
For people with Prader-Willi syndrome, the world is full of food they cannot safely eat, and the drive to eat it never lets up. Kathlene Jones, chief executive of the Prader-Willi Research Foundation Australia, describes it as relentless pressure that brings great distress and very challenging behaviours, and that reaches the whole family.
Researchers at the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne now report a way to switch back on healthy genes that are silenced in the condition. If it holds up, it could lead to treatments aimed at the cause of the disorder rather than its symptoms. The work was published in Science Advances.
About 400,000 people worldwide live with Prader-Willi syndrome, a complex genetic condition that affects the brain. It brings lifelong physical and developmental challenges, including developmental delay, intellectual disability and an insatiable appetite that can lead to obesity. Many people with the condition depend on multiple medications, surgeries and specialist care. Those treatments manage symptoms, and the relief they give is limited.
The study centres on SMCHD1, a protein WEHI discovered in 2008. It helps regulate gene activity. In Prader-Willi syndrome it acts as a kind of genetic brake, keeping certain genes that matter for development and brain function switched off.
The team used CRISPR gene editing, stem-cell and genomic technologies to follow what happened when SMCHD1 was removed. They measured the effects across thousands of genes and in the brain tissue most relevant to the disease. In patient-derived cells and in animal models, taking away the protein released the brake and the dormant genes came back on. WEHI describes the study as a world first.
Professor Marnie Blewitt, WEHI's Deputy Director and head of its epigenetics laboratory, led the work. She says the central question was always safety, because any eventual treatment would target babies and young children. "We thought reactivating the 'sleeping' genes might be possible – what we didn't know was whether we could do it safely," she said. In her words, the team now has the strongest evidence yet that removing SMCHD1 can restore the lost gene activity without disrupting the rest of the body.
Blewitt works closely with affected families. She has seen children undergo multiple surgeries for scoliosis, and has met families whose lives revolve around medications, specialist appointments and managing symptoms that are often life-threatening. For her, the result caps nearly two decades of work that began with the discovery of SMCHD1. "This is my life's work," she said, calling it incredibly rewarding to see the approach succeed.
Families helped make the research possible. The Prader-Willi Research Foundation Australia and the Foundation for Prader-Willi Research USA both supported the study, and both were founded and led by families affected by the condition. Jones called the findings an important step and said a treatment addressing the root cause would be transformational, though she stressed the work is still at an early stage. Other funders included the National Health and Medical Research Council, WEHI innovation funding, the Rebecca L. Cooper Medical Research Foundation, the Pamela and Lorenzo Galli Trust, the Brian M Davis Charitable Trust and the Australian Government Research Training Program, with infrastructure support from the Victorian Government.
The next stage has already begun. Togglelux Therapeutics, a Melbourne-based WEHI spinout focused on disease-modifying treatments for Prader-Willi syndrome, is developing the approach into potential medicines. What to watch is whether the safety seen in cells and animal models carries over to the youngest patients, who would be the intended recipients.
Citazioni salienti
We thought reactivating the 'sleeping' genes might be possible – what we didn't know was whether we could do it safely.— Professor Marnie Blewitt, WEHI
A treatment that addresses the root cause of the disease would be transformational, though the work is still at an early stage.— Kathlene Jones, CEO, Prader-Willi Research Foundation Australia (paraphrased)
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