From gene discovery to therapies for rare disease a research - PowerPoint PPT Presentation

From gene discovery to therapies for rare disease – a research perspective A/Prof Carol Wicking Director, IMB Centre for Rare Disease Research, UQ Rare Disease Summit 2015 Melbourne 27-28 March

• Why rare disease? • Why now? • Why IMB/UQ/Australia?

Why rare disease? • Importance of rare diseases in their own right • Research on rare diseases will impact common diseases

Gorlin’s syndrome • Rare inherited cancer predisposition syndrome • Gene Patched1 – hedgehog signalling pathway • Also responsible for common sporadic forms of BCC • First BCC drug (Erivedge or FDA Approves Drug for Basal Cell Carcinoma vismodegib) approved by the FDA in 2012 www.cancer.org › Learn About Cancer › News and Features › News

Temple-Baraitser Syndrome • Intellectual disability, epilepsy, hypoplasia of the nails of the thumb and great toe • Originally 7 known cases worldwide, now 16 • Potassium channel

Why now? Cystic fibrosis – 1989 Prior to genome project 5 years from linkage to gene, many groups worldwide

• Skeletal ciliopathies • Whole exome sequencing trios • Weeks-months • 5 novel disease genes since 2013

Advances in genome editing: CRISPR/Cas9 • ability to rapidly modify the genome of model organisms and cells (iPS) • Mice – Peter Koopman • Zebrafish – Ben Hogan, Kelly Smith

The zebrafish as a model for human disease Kelly Smith Ben Hogan Kaufmann et al., 2012

IMB Centre for Rare Disease Research • Genomics; leukodystrophies – Cas Simons • Ciliopathies/skeletal dysplasia - Carol Wicking • Congenital heart disease – Kelly Smith • Lymphoedema – Ben Hogan, Mathias Francois • Disorders of sex development – Peter Koopman (Andrew Sinclair MCRI) • Rare brain cancers – Brandon Wainwright • Renal disease – Andrew Mallet (RBH), Melissa Little (MCRI) • UQ Diamantina Institute – Matt Brown, Emma Duncan • MCRI – Melissa Little, Andrew Sinclair

IMB CRDR and Genetic Health Queensland • Julie McGaughran, Michael Gabbett (GHQ) and Cas Simons (IMB) • Sequencing unsolved dysmorphology cases

IMB Centre for Rare Disease Research Sequencing/Gene discovery Known disease gene Novel disease gene Model in zebrafish, mice, cells Therapy development, drug screening platforms