The National Referral Laboratory (http://www.wch.sa.gov.au/services/az/divisions/labs/geneticmed/nrl.html) provides diagnostic service provisions for patients with inherited metabolic disorders. Our primary research goal is to improve the efficiency of diagnosis, understand pathology and investigate therapeutic strategies. In particular, the laboratory's interest lies in inherited brain disorders which despite presenting throughout life, disease burden is greatest in childhood. Neurological regression is relentless with a loss of acquired skills such as the ability to speak, walk, eat, and has a devastating impact on the child and family. There are no cures and as yet no treatment for the progressive decline in brain function.

Gene therapy has been touted for treating such diseases by replacing the defective gene with a functional one. Our laboratory is involved in gene therapy clinical trials by measuring disease biomarkers from enrolled patients to assess therapeutic efficacy of the gene therapy treatment. However, as therapy begins following diagnosis, when patients are symptomatic, treatment is challenged with reversing pathology that is already entrenched. At best then, treatment may only be able to halt disease progression and stabilise the disease.

To address this we are performing a number of parallel studies in mouse and cell models of these genetic disorders, to learn more about the progression of the neurological process and the irreversibility of disease. Biomarkers of disease activity can then be translated into our diagnostic pathology service for use in patients. Studies in cell models, including neuronal cultures, can inform on mechanisms of disease to learn more about the neurodegenerative decline and open up new avenues for treatment and adjunct therapies to complement gene therapy approaches. The laboratory has a number of higher degree research projects in these areas to join three post-doctoral scientists working in these areas.