New research from Australia has demonstrated that genes silenced in Prader-Willi syndrome can be switched back on, opening an exciting potential avenue for treating the underlying cause of the condition. Importantly, the findings also suggest that treatment may not need to be restricted to babies and very young children.
A new study from the Walter and Eliza Hall Institute of Medical Research (WEHI) in Australia, published in the peer-reviewed journal Science Advances in October 2026, represents an important step towards that ambition.
What is particularly exciting about this study is that rather than targeting individual symptoms, researchers have identified a potential way to address the underlying genetic problem responsible for PWS.
What have researchers discovered?
PWS occurs when certain genes on chromosome 15, normally active on the chromosome inherited from the father, are not functioning. People with PWS still possess corresponding genes inherited from their mother, but these are naturally switched off through a process known as genomic imprinting.
Researchers have identified a protein called SMCHD1, which helps keep these maternal genes switched off. By removing SMCHD1 in laboratory experiments, they were able to reactivate previously silent genes.
Crucially, this was demonstrated in both human cell models, including cells derived from people with PWS, and mouse models. This is particularly significant because it suggests a possible way of treating the genetic cause of PWS rather than simply managing its symptoms.
Could treatment benefit older children and adults?
One of the most encouraging aspects of the published research concerns the timing of gene reactivation. Naturally, families with older children, teenagers and adults may wonder whether a future treatment would arrive too late to make a meaningful difference. The study provides several reasons to believe that gene reactivation may remain possible beyond the earliest stages of development.
Firstly, researchers demonstrated that removing SMCHD1 after certain early developmental processes had already occurred could reactivate PWS-related genes in mice. Secondly, they successfully reactivated genes in brain tissue, including the hypothalamus, an area particularly relevant to PWS because of its role in appetite, metabolism and other bodily functions. Thirdly, researchers attempted to remove SMCHD1 during the first week after birth in mice. Although technical difficulties limited this experiment to two surviving animals, they observed some reactivation of a previously silent gene. Finally, the researchers demonstrated improvements in several PWS-related characteristics in their mouse model, including aspects of muscle function, body weight and social behaviour. These findings are important because they suggest that restoring gene activity could potentially improve aspects of PWS, rather than only preventing difficulties from developing in the first place.
An important qualification
The study does not demonstrate that treatment will be equally effective at every age.
Most of the successful experiments involving brain function and improvements in symptoms used mice in which SMCHD1 was removed during embryonic development, although the animals were assessed later. The postnatal experiment provides additional encouragement, but it did not establish whether treating older animals could reverse established symptoms. Nevertheless, the research challenges the assumption that gene reactivation must necessarily take place at the very beginning of life. This provides a strong scientific reason to investigate whether future treatments could benefit older children and adults.
Did researchers observe improvements in PWS symptoms?
Yes, although the results require careful interpretation. In a mouse model involving loss of the PWS-related gene Magel2, researchers observed improvements in several characteristics associated with the condition. However it is important to recognise that a mouse model involving one PWS-related gene cannot reproduce the full complexity of PWS in humans. Nevertheless, these findings represent an important step beyond simply demonstrating that genes can be switched back on. They provide early evidence that gene reactivation can translate into meaningful improvements in functioning.
What about safety?
One of the major challenges with treatments designed to reactivate genes is ensuring that they do not unintentionally interfere with other important genetic processes. SMCHD1 plays a role in regulating several groups of genes, so removing it could theoretically have unwanted consequences. Encouragingly, researchers found relatively few unintended changes in gene activity when SMCHD1 was removed after certain early developmental stages. The mice also generally remained healthy into adulthood. This suggests that targeting SMCHD1 may offer a relatively selective approach to gene reactivation.
However, these findings do not establish that a future medicine would be safe in humans. Extensive additional research and clinical trials would be required.
How soon might a treatment become available?
The research remains at a preclinical stage. Although scientists have demonstrated that removing SMCHD1 can reactivate genes, they still need to develop a medicine capable of safely producing the desired effect. The findings are now being advanced towards potential therapies through Togglelux Therapeutics, a biotechnology company established from WEHI research. This is an encouraging development, but there is currently no established timetable for human trials or an approved treatment.
Why this research matters for the PWS community
For many families, the ultimate ambition is not necessarily a complete cure. A treatment that substantially reduces some of the most challenging aspects of PWS could make an enormous difference to quality of life. Improvements in appetite regulation, physical functioning, behaviour or cognitive abilities could potentially increase opportunities for education, employment, relationships and greater independence. It is important to stress that this particular research has not yet demonstrated improvements in all these areas. They represent possible longer-term ambitions for treatments that address the underlying genetic cause.
The wider significance is that researchers are increasingly exploring approaches that might change the course of PWS itself. And importantly, this new study offers reasons to investigate whether such treatments could benefit people who are already beyond early childhood.
Reasons for cautious optimism
This is not a cure, nor is it evidence that an effective treatment is just around the corner. There remain substantial scientific challenges, including developing a suitable drug, establishing its safety and demonstrating meaningful benefits in people with PWS.
However, the researchers have achieved something significant: they have demonstrated that previously silent PWS genes can be reactivated, including in relevant brain tissue, and that this can improve some PWS-related characteristics in mice.
Perhaps most encouragingly for families with older children and adults, the findings suggest that the opportunity for gene reactivation may not be confined to the earliest stages of life.
For now, it represents a genuine scientific advance and another important reason for the PWS community to look towards the future with cautious optimism.
Further reading
Original peer-reviewed research:
Iminitoff M. and colleagues (2026). SMCHD1 is a target for gene activation therapy to treat Prader-Willi syndrome. Science Advances, 12(41), eaej5702.
https://doi.org/10.1126/sciadv.aej5702
WEHI research announcement: