Latest findings and a spin-off company from the Blewitt lab at WEHI (Walter and Eliza Hall Institute of Medical Research), Melbourne

Research that PWRFA has been proud to support has reached an important milestone. A new preprint on bioRxiv from Professor Marnie Blewitt's laboratory at WEHI — led by Dr Meg Iminitoff — reports the most comprehensive evidence yet that a protein called SMCHD1 is a viable target for gene-activation therapy in PWS.

The core idea is elegantly simple: every person with PWS carries a silent but intact copy of the affected genes, inherited from their mother. SMCHD1 acts as a molecular "off switch" keeping those genes quiet. Remove SMCHD1, and those genes can wake up.

What the team found

The results described in the bioRxiv pre-print confirm this strategy works — in human cells and in living mice — and builds significantly on earlier findings the team have shared with the PWRFA community.

In neural cells derived from PWS patients, and in the mouse brain, removing SMCHD1 activated the typically silent maternal genes across the entire PWS cluster. This approach enabled partial restoration of gene expression, with earlier intervention producing stronger effects at some genes.

Crucially, this reactivation was still effective when SMCHD1 was removed after early brain development — the timing that would matter most in a real treatment setting.

Measurable improvements in multiple phenotypes were recorded in a mouse model of PWS which had SMCHD1 deleted from the brain, despite incomplete PWS gene activation:

· In female mice, around half showed full normalisation of body weight — and in that group, grip strength and motor coordination also improved significantly.

· Both male and female mice showed a full rescue of a social behaviour abnormality — During their normal active period, PWS mice spent less time separated from other cage mates, a pattern that normalised when SMCHD1 was deleted.

· Finally, a trend toward improvement in day/night activity patterns was observed, this is potentially relevant to the sleep disturbances common in PWS, although the authors note that larger studies will be needed to confirm this finding.

On safety, genome-wide analysis detected very few unintended changes in gene expression. The SMCHD1-deleted mice survived normally into adulthood. The team also confirmed the approach is unlikely to inadvertently trigger Angelman Syndrome at the levels of gene activation currently achieved.

Why this matters - A spinout company

This paper is the product of years of sustained, methodical work — spanning patient-derived cell models, mouse genetics, brain tissue sequencing, molecular imaging, and behavioural testing across two independent animal cohorts. Findings of this depth and rigour don’t emerge from a single funding cycle.

This research has a direct line to the clinic. The sustained investment in Marnie's team's work has recently resulted in the creation of Togglelux Therapeutics — a spinout company from WEHI dedicated to targeting SMCHD1 as a treatment for PWS. The science in this bioRxiv preprint is the foundation that makes a company like Togglelux possible. It is a tangible reminder of what long-term research funding can achieve — and PWRFA is proud to have played a role in that journey.

Iminitoff et al., bioRxiv preprint, May 2026. Not yet peer-reviewed.

https://www.biorxiv.org/content/10.64898/2026.05.13.725051v1