None listed
Conditions
Brief summary
Motor neuron disease (MND) is a rapidly-progressive and fatal neurological condition. There is no cure. Riluzole, the only available treatment, has a very modest benefit at best. Diagnosis is often delayed. CuATSM (‘copper ATSM’) is a compound that has been shown to protect against a type of newly-described cell death known as ferroptosis in animal models of MND. The results of a recent phase 1 trial of CuATSM in humans with MND were promising. Additionally, radiolabelled CuATSM was detected via PET imaging in parts of the brain involved in MND in a pilot study. CuATSM may therefore be disease modifying as well as localising to areas of active disease, showing promise both as a treatment and diagnostic agent. This project is an imaging study which aims to further explore the role of CuATSM in diagnostic imaging. We aim to use radiolabelled 64CuATSM PET in conjunction with a type of MRI scanning called quantitative state mapping, which detects iron in the brain, another potential marker of ferroptosis. Participants will have these scans at baseline. Clinical data, including neurological examination and cognitive testing results, will be collected. We aim to explore whether both types of imaging demonstrate involvement of the same brain regions. Positive results would 1) provide evidence that the type of cell death known as ferroptosis is occurring in humans with MND, 2) support ongoing clinical trials of anti-ferroptotic agents such as CuATSM, and 3) support future exploration of these imaging techniques in diagnosis and monitoring of disease progression.
Interventions
This is a cross-sectional exploratory neuroimaging biomarker study. Following informed consent, clinical data (diagnosis, disease parameters, cognitive data) will be obtained. Participants will have one brain PET/MRI scan which will be acquired at Monash Biomedical Imaging in Clayton, VIC. PET imaging will consist of a an intravenous bolus of up to 200 MBq of 64Cu(ATSM) over 60s followed by up to 90min dynamic acquisition of the PET image. MRI imaging will comprise both a volumetric image and
This is a cross-sectional exploratory neuroimaging biomarker study. Following informed consent, clinical data (diagnosis, disease parameters, cognitive data) will be obtained. Participants will have one brain PET/MRI scan which will be acquired at Monash Biomedical Imaging in Clayton, VIC. PET imaging will consist of a an intravenous bolus of up to 200 MBq of 64Cu(ATSM) over 60s followed by up to 90min dynamic acquisition of the PET image. MRI imaging will comprise both a volumetric image and a quantitative susceptibility mapping (QSM) image acquired during the same session. Blood will be collected for measurement of other markers of neurodegeneration and oxidative stress, including neurofilament light chain, isoprostanes, and acute phase proteins. Imaging will be conducted by trained staff at Monash Biomedical Imaging. Clinical data will be collected by study physicians.
Sponsors
Florey Institute of Neuroscience and Mental Health
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Diagnosis
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
limb onset variant of motor neurone disease / amyotrophic lateral sclerosis
Exclusion criteria
1) presence of other known neurological or psychiatric diseases which may cause MRI changes 2) history of learning disability / intellectual disability 3) unable to tolerate PET or MRI scanning 4) diagnosis of dementia
Outcome results
None listed