Steyn Group - Projects
The Metabolic Exploration in Neurodegenerative Disease (MEND-MND) program
Derangements in process that regulate metabolic health are central to many diseases and can greatly impact the survival and quality of life of patients. Working in close collaboration with Associate Professor Shyuan Ngo at AIBN we are creating new knowledge to improve our understanding of how negative energy balance impacts disease progression. In patients we found that increased resting metabolism is associated with faster disease progression and earlier death, whereas our preclinical studies suggest that these changes in metabolism could occur because of changes in substrate preference.
Knowledge gained from these studies will allow us to identify novel targets that we can modify to help the body to sustain optimal energy needs throughout the course of disease. Ultimately, this will help us to develop rational strategies to improve energy balance in MND, which will ultimately improve prognosis for patients with MND. Most recently, our observations from the MetFlex clinical trial – and investigator initiated and conducted, multicentre, international, open-label, single-arm, Phase 2a showed that the drug Trimetazidine is safe in ALS, and can lower metabolic markers and markers of oxidative stress.
As part of our long-term vision to improve understanding of the causes for hypermetabolism in MND, we initiated new projects with Prof Rod Minchin and the Minchin Group, focussing on endogenous factors with potential to change mitochondrial responses to disease. Here we are using mouse and cell models of disease, as studies begin to unravel the role of NAT1 as a possible modulator of the metabolic response to disease.
The Endocrine and Appetite Targets and Therapies FOR the treatment of MND (EATT4MND) program
The EATT4MND research program evolved from clinical research observations showing that some patients with MND experience unexplained loss of appetite. We also found that changes in endocrine factors in patients with MND, including a reduction in a hormone best known for its role in stimulating appetite. This hormone is involved in a range of processes throughout the body, and modulation of the pathways associated with this hormone has potential to treat the pathophysiology of MND.
The EATT4MND project covers two broad areas of research:
- Studies to improve our understanding of the factors that contribute to the loss of appetite in MND, and how loss of appetite might impact disease heterogeneity.
- Studies that target endocrine factors to slow disease progression.
As part of our efforts to improve understanding of the cause and impact of loss of appetite, we are conducting imaging studies at the Herston Imaging Research Facility (HIRF) to identify structural and functional derangements within appetite centres of the brain of people with MND. Clinical studies also investigate the impact of MND on the gut microbiome. Some of our recent results suggest that changes in appetite in patients with ALS could negatively impact microbiome diversity, however that this might favour slower disease progression.
As part of our efforts to improve our understanding of the impact of MND on endocrine factors known to modulate energy balance, we have initiated studies that seek to target these factors to slow disease progression. Working in collaboration with industry, and using multiple mouse and cell models of disease, we are now testing compounds that mimic the effects of hormones with potential to modulate appetite and metabolism as a treatment for MND. This includes compounds that target multiple disease-relevant pathways to determine if they can slow disease progression across the broad spectrum of MNDs.
The Biomarkers in slow progressing and LONG surviving forms of MND (B-Long) program
The BeLong research program aims to improve our understanding of factors that impact disease progression in patients with upper or lower motor neuron dominant forms of disease. While lifespan may not change in patients with slow progressing forms of MND, there is an urgent need to develop earlier diagnostic tools and improved strategies to help patients maintain better quality of life.
As part of the BeLong research program we are exploring unique biomarkers that could help identify and monitor the progression of these variants of disease. Building on studies in blood biomarkers, and through a new partnership with Dr Thomas Shaw, Professor Markus Barth and the Centre for Advanced Imaging, the BeLong program will match detailed clinical phenotypes of patients with Ultra-High Field (UHF/7 Tesla) MRI imaging studies of the brain and spinal cord.
The Digital technology in ALS (DIGITALS) program
Working with Associate Professor Shyuan Ngo (AIBN) and researchers from the Netherlands and the UK, the DigitTALS initiative seeks to improve our understanding of the use of digital technologies in improving care for people living with MND. This is critical, as the collection of large amounts of information in the real world will improve our capacity to make sense of variability across people living with MND.
Central to this project is our engagement with patients, as they direct the development of digital technologies that will suit them most. Digital technologies may also provide opportunities to improve clinical trial design.
Here we are exploring the use of wearables in providing real-time and high-resolution data that might inform safety and efficacy studies. Our studies show that these technologies can offer improvements over existing clinical outcome measures commonly used in ALS-specific clinical trials.
The UnBurden research program
In collaboration with Dr Rebecca Packer (UQ), the UnBurden program seeks to improve our understanding of the lived experience of people with MND, with a particular focus on the challenges faced by both patients and their carers. By exploring how individuals navigate the complex physical, emotional, and logistical burdens of the disease, this program aims to identify strategies that can support day-to-day wellbeing.
A key element of UnBurden is the co-design of solutions with the MND community. For example, in partnership with the MND and Me Foundation, we recently evaluated the use of the MND-PRISM app - a digital tool designed to help people manage the daily complexities of living with MND. This work is helping us to better understand how technology and tailored support can reduce the practical and emotional toll of the disease.