Activating SMCHD1 to treat Facioscapulohumeral muscular dystrophy

Activating SMCHD1 to treat Facioscapulohumeral muscular dystrophy

The opportunity

  • There is currently no specific treatment available for Facioscapulohumeral muscular dystrophy (FSHD), a genetic muscle disorder caused by abnormal expression in adult cells of the transcription factor DUX4
  • SMCHD1 is an important repressor of DUX4 that possesses enzymatic (ATPase) activity; altered ATPase activity of SMCHD1 has been shown in disease
  • SMCHD1 activation is a potential FSHD therapy

FSHD is a genetic muscle disorder mostly affecting muscles of the face, shoulder blades and upper arms. It is estimated to affect about 1 in 7500-20,000 individuals worldwide. FSHD is caused by DUX4 expression, which is normally silenced in adult cells by SMCHD1 and other epigenetic repressors.


Scientific diagram


The technology

We have shown that SMCHD1 contains a GHKL-ATPase domain and confirmed that it possesses enzymatic activity. Decreased ATPase activity has been found in FSHD patients suggesting that activation of SMCHD1 activity could be a potential FSHD therapy.

Opportunities for partnership 

We are seeking a partner to co-develop SMCHD1 activators for FSHD therapy.

We have:

  • Foremost experts in SMCHD1, a world class structural biology program and an understanding of SMCHD1 structure  
  • High quality recombinant protein, validated screening assays and capability for structure-guided medicinal chemistry

We are seeking a partner:

  • To invest in our medicinal chemistry program to follow up identified hits from an ongoing fragment-based drug discovery campaign
  • With culture systems of human muscle cell systems to validate activator hits

Scientific team

Professor Marnie Blewitt, Head, Epigenetics and Development division
Associate Professor James Murphy, Head, Inflammation division


Dr Anne-Laure Puaux, Head, Biotechnology and Commercialisation

Phone: +61 3 9345 2175