Genomic Medicine Genomics
Project 2
Precision therapies for life-threatening rare genetic diseases in children Developing personalised medicines using genomics, stem cells and drug screening to restore brain function in children with rare, life-threatening genetic disorders. Problem Each year, around 15,000 Australian children are born with rare genetic diseases. TRAPPC4 Deficiency and CDKL5 Deficiency Disorder (CDD) are two such rare genetic diseases, affecting up to 1 in 40,000 births. They cause drug-resistant epilepsy seizures, severe intellectual disability, dementia and profound mobility issues. These devastating conditions have health impacts comparable to quadriplegia and treatment options are limited. Solution Current treatments for TRAPPC4 and CDD only manage symptoms rather than address root causes. Our team is focusing on identifying new treatments for these ‘incurable’ conditions. We use stem cells and ‘mini brain’ organoids to study these genetic diseases and to look for treatments.
a) High throughput drug screening for CDD This project focuses on conducting high throughput drug screening of thousands of existing drugs to identify potential new treatments for CDD. We use a combination of advanced imaging approaches and electrical measurement techniques in brain cells (neurons) and mini brain organoids to identify the best drug candidates. This will accelerate the development of precision therapies and identify new treatments for CDD.
Rare disease Stem cell medicine
Investment required AU$210,000 Some research projects will require additional funding for future phases of the research and can be scaled up to have an even greater impact. Research lead Dr Nicole Van Bergen
b) Personalised medicine for TRAPPC4 deficiency. Nearly all patients with TRAPPC4 deficiency have the same ‘genetic mistake’. Antisense oligonucleotides (ASOs) represent a new and highly promising class of drugs for personalised medicine. We have developed an antisense oligonucleotide (ASO) treatment that has the potential to be applied to nearly all TRAPPC4 deficiency patients. We have already shown our ASO to be effective in patient cells, and it has passed all safety testing to date. One of the last remaining steps is to test our lead ASO in mini brain organoids to make sure it is effective in brain cells. This treatment promises to provide an effective and safe treatment for TRAPPC4 deficiency patients.
Each year, around 15,000 Australian children are born with rare genetic diseases.
30
Murdoch Children’s Research Institute