Treating inherited brain disease in children

This genetics and molecular pathology project explores the use of gene therapy to treating inherited brain disease in children.

Inherited brain disorders present throughout life although disease burden is greatest in childhood. Neurological regression is relentless with a loss of acquired skills – e.g. the ability to speak, walk, eat - and a devastating impact on the child and family. 

There is no cure and as yet no treatment for the progressive decline in brain function. 

Gene therapy has held promise for treating such diseases by replacing the defective gene with a functional one. The first-in-man gene therapy trial for the inherited neurodegenerative disease known as mucopolysaccharidosis type IIIA (MPS IIIA) is underway with patients currently treated in the USA, Spain and Australia. 

Our laboratory is heavily involved with this trial by measuring disease markers from these patients to assess therapeutic efficacy of the gene therapy approach. MPS IIIA is often considered the prototype for inherited neurodegenerative metabolic disease and, like all of these diseases, is progressive. This means that any treatment – including the aforementioned gene therapy trial – is challenged with treating residual pathology that is already well-established and considered irreversible. At best then, treatment may only be able to halt disease progression and stabilise the disease.

This project will performing a parallel study in an authentic mouse model of MPS IIIA, in which brain tissue can be examined, we will learn more about the progression of the neurological process and the irreversibility of disease. To do this, gene therapy vectors will be administered to MPS IIIA mice at different ages, representing different stages of residual disease burden, and the brains removed for biochemical testing. 

These same tests will be performed on cerebrospinal fluid collected from the human trial to evaluate the biochemical changes seen in the mice model with the human patients. Memory and learning will also be evaluated in these mice. 

The outcome will inform on the timing and efficacy of treatment as well as explore sites for therapeutic intervention to address existing pathology that is not reversible with the gene therapy approach.

Gene therapy trial information


Tagged in Honours projects - Molecular and biomedical science, Honours projects - Chantelle McIntyre, Honours projects - Molecular and biomedical science: Genetics, Honours projects - Maria Fuller