The Bioengineering & Molecular Medicine Research Group focuses on two key areas of research: Brittle Bone Disease and Neurofibromatosis.
Brittle Bone Disease
Brittle Bone Disease or Osteogenesis Imperfecta (OI) is a genetic condition that predisposes individuals to bone fragility. While careful clinical management can minimise the number of fractures a patient will get, there is currently no cure for the condition.
“Our team is investigating pharmaceutical treatments to reduce fracture risk in individuals with brittle bones, to improve their quality of life. However, there is also the potential to use emerging gene therapy methods to correct mutations at the genetic level – affecting a lasting cure.”
Our team has published extensively on drug therapies for OI, most recently examining the combination between bisphosphonates and growth hormone.
Projects
There are several key projects underway in the Brittle Bone Disease Research team.
- Gene targeting for brittle bone disease
Brittle bone disease is caused by mutations most commonly in the type I collagen genes, but there are over a dozen other genes that can cause rarer causes of the condition. Advances in CRISPR gene editing combined with bone-targeting vectors we have designed are being used to create therapeutic vectors for future human trials. Curative gene therapy has a remarkable potential for bone disorders.
- Drug therapies for brittle bone disease
We have assessed the utility and interactions between different drugs in preclinical models of bone healing. Key drugs include bisphosphonates, romosozumab (anti-sclerostin Ab), and growth hormone, however our team is exploring other options in the pharmaceutical space.
Funding & Collaborations
Our Brittle Bone Research program has been supported by the Australian Paediatric Endocrine Group (APEG), the Teicke Foundation, and the Sydney Children’s Hospitals Network Foundation.
Key collaborators include Prof Craig Munns (Queensland Children’s Hospital) and Prof Christopher Little (Royal North Shore Hospital).
Student Opportunities
GENE THERAPY FOR BRITTLE BONE DISEASE (PHD PROGRAM, USYD)
https://www.sydney.edu.au/research/opportunities/3415.html
Neurofibromatosis Research
Neurofibromatosis type 1 (NF1) and Neurofibromatosis type 2 (NF2) are genetic conditions that present with major challenges for clinical management. In NF, gene mutations cause tumours to form on nerve tissues. This can result in frequent small tumours just below the skin (cutaneous and subcutaneous neurofibromas), larger plexiform neurofibromas and more severe tumours including optic gliomas and MPNSTs. Individuals can face a range of other challenges including orthopaedic complications, muscle weakness, and specific learning difficulties (NF1) as well as unilateral or bilateral hearing loss (NF2).
“Our team is committed to developing new treatments for NF1 and NF2, with a particular focus on gene therapy. Current treatments for NF are largely symptomatic – they help manage clinical challenges as they arise. By using vectors that can fix the genetic mutations in affected cells (nerve cells and other tissues), we hope to prevent symptoms of the disease from manifesting in the first place.”
Projects
There are several key projects underway in the Neurofibromatosis Research team.
- Gene targeting for NF1 and NF2
Neurofibromatosis types 1 and 2 are caused by a range of mutations in the genes encoding neurofibromin and merlin respectively. Our team is developing targeted AAV vectors integrating CRISPR technology able to repair the mutations at the genetic level.
- Carnitine therapy for NF1
Carnitine is a nutraceutical supplement that has been shown to ameliorate muscle weakness and fatigue in mouse models of NF1 and more recently in early clinical trials. We are planning to expand into adult trials and develop educational tools regarding the potential benefits of carnitine therapy.
Funding & Collaborations
Our Neurofibromatosis Research program has been supported by the National Health and Medical Research Council of Australia, the Children’s Tumor Foundation (US), and the Flicker of Hope Foundation.
Key collaborators include Dr Samantha Ginn (Children’s Medical Research Institute), Dr Gaetan Burgio (Australian National University), Dr Yemima Berman (Royal North Shore Hospital) and Dr Gabriel Dabscheck (Murdoch Children’s Research Institute).
Recent Achievements
- Brittle Bone Disease: Excitingly, our team has developed a gene therapy vector that is able to target bone cells specifically, and have recently used this to show proof-of-principle that it can be used to improve bone growth and strength.
- Neurofibromatosis: Our team has a track record of developing clinical treatments for NF1. Basic research has led to successful clinical trials for the treatment of tibial non-unions using adjunctive drug therapies alongside orthopaedic surgery and for the use of the nutritional supplement carnitine to improve muscle performance in children with NF1.
Brittle Bone Disease Researchers
Postdoctoral Fellow: Dr Alexandra O’Donohue
PhD Students
- Christal Au-Yeung
- Julian Chu
Neurofibromatosis Researchers
Postdoctoral Fellow: Dr Alexandra O’Donohue
PhD Student: Hsien-Yin Kao