Our research includes using a model of Huntington’s disease where we are following up our discoveries regarding the beneficial effects of environmental enrichment (enhanced cognitive stimulation and physical activity) and exercise, to identify potential new therapies.  Using a transgenic mouse model of HD, our group has made progress in understanding changes that lead to cognitive, psychiatric and motor symptoms.

We were the first group to demonstrate depression-like behaviors in a preclinical model of HD, and the first to relate cognitive dysfunction to in vivo deficits of experience-dependent brain plasticity. We were also the first to show that environmental factors, including environmental enrichment, exercise and stress, can modify onset and progression of HD.  Most recently, we discovered that the trillions of bacteria living in the gut are abnormal in HD mice (this is called ‘gut dysbiosis’), and this discovery has been translated by Melbourne colleagues.

Our ongoing research aims to use this model of HD to identify novel targets for new therapies.  We use cutting-edge technologies to identify key molecules that we can target with candidate therapies, including novel drugs.  We then use this preclinical model of HD to test these therapies.  Promising candidates can then be progressed to clinical trials.

For further information about the study please contact:

Professor Anthony Hannan

Florey Institute of Neuroscience and Mental Health

Email: [email protected]

Website:  Professor Anthony Hannan – Florey

Our laboratory has extensively contributed to our understanding of gene-environment interactions in Huntington’s disease (HD), including the beneficial effects of cognitive stimulation and physical activity. Environmental enrichment and exercise interventions mimics a stimulating lifestyle, which has been shown to positively impact different neurodegenerative conditions, including HD, where Anthony Hannan and colleagues made the original discoveries. These approaches have been able to ameliorate neurodegenerative phenotype, emotionality-related behaviours and cognitive effects in HD transgenic mice. We are interested in this project to understand the promising actions of these interventions on the differential gut microbial profile (microbiome) presented in HD mice, also previously discovered by the Hannan Laboratory at the Florey Institute. To achieve this goal, we use cognitive and behavioural tasks, as well as genetics, genomics and bioinformatics tools.  These results will be crucial to our understanding of the physiological role of these environmental interventions on gut microbial profile in HD, and will help us identify new therapeutic targets to delay onset and progression of this devastating disease.

Applications of computational modeling in Huntington’s disease is a promising avenue in research directing towards predicting the disease progression. In the past few years, researchers have shown the positive impacts of modeling the disease progression to find the most sensitive biomarkers not only in Huntington’s disease but also in other neurodegenerative disease such as Alzheimer’s’ disease. We are interested in applying computational modeling techniques to the combined data sets from IMAG-HD, PREDICT-HD and TRACK-HD studies to find a model that could explain the disease progression across studies with high accuracy. In the process of developing the model we aim explore and incorporate not only the clinical measures but also the behavioral and imaging measures and find the best combination of measures that results in the highest predictability of disease progression. These modelling techniques will be crucial to understand the level of contribution of each measure to disease progression which then can be used in the advancement of developing more effective treatment methods or therapeutical approaches targeting the most sensitive measures, to delay the neural degeneration and the subsequent onset of the Huntington’s disease.

Hiba is a Clinical Neuropsychology PhD student at Monash University, and is completing her doctoral project in the Stout lab. Hiba loves being out in nature and spends her weekends going on long walks or drives to scenic areas (when lockdown permits!). She also enjoys travelling and is determined to visit Turkey as soon as the borders open!

As part of her research, Hiba is investigating the experience of depression in people with Huntington’s disease and the factors linked to depression in this population. Hiba is about to finish recruiting for this study and hopes to share her findings with the broader HD community very soon.