Precision epigenetics: silencing SMCHD1 to treat Prader Willi Syndrome

Precision epigenetics: silencing SMCHD1 to treat Prader Willi Syndrome

The opportunity

  • There is currently no treatment available that targets the genetic cause of Prader-Willi Syndrome (PWS)
  • We showed that Smchd1 deletion in committed cells causes selective gene reactivation at the PWS cluster
  • Seeking partners to progress the development of SMCHD1 inhibitors as a potential PWS therapy

PWS occurs due to mutations in the paternal allele causing a failure to express critical genes. It affects 1 in 10,000 newborns and medical care per patient is between $30-66,000 annually.

Current treatments target symptoms instead of the genetic cause of PWS. 


Scientific illustration

The technology

SMCHD1 represses PWS critical genes on the maternal allele.


Scientific illustration


We showed selective gene reactivation of PWS genes following genetic deletion of Smchd1, suggesting that SMCHD1 could be a potential PWS therapy target (Table 1). 


Table 1: Selective gene reactivation from Smchd1 deletion

Smchd1 binding sites


Committed cell

Hox clusters

Failed silencing

Silencing maintained

X Chromosome

Failed silencing

Silencing maintained

PWS cluster

Failed silencing

Gene reactivated (maternal allele)


Opportunities for partnership 

We are seeking partners to co-develop SMCHD1 inhibitors. 

We have:

  • Foremost experts in SMCHD1, a world-class structural biology program and an excellent understanding of SMCHD1 
  • A lead SMCHD1 inhibitor and in vitro neural cell assays to conduct initial testing

We are seeking investments to:

  • Enable the in vivo validation of SMCHD1 inhibition in PWS mouse model
  • Expand on proof-of-concept experiments in patient iPSC-derived hypothalamic neurons
  • Further progress lead optimisation for our SMCHD1 inhibitor medicinal chemistry program

Scientific team

Professor Marnie Blewitt, Division Head, Epigenetics and Development division

Associate Professor James Murphy, Division Head, Inflammation division


Dr Anne-Laure Puaux, Head, Biotechnology and Commercialisation

Phone: +61 3 9345 2175