MJFF Circuits and Cellular Targets for Parkinson’s Symptoms – Pre-Clinical Program
Closing Date: 27/09/2022
Grants to further understand the biological substrates and pathophysiological mechanisms that contribute to Parkinson’s disease with pre-clinical models.
Established in 2000, the Michael J Fox Foundation (MJFF) was set up to find a cure for Parkinson’s disease (PD) and ensure the development of improved therapies.
The goal of the MJFF Circuits and Cellular Targets for Parkinson’s Symptoms – Pre-Clinical Program is to further the understanding of the biological substrates and pathophysiological mechanisms that contribute to PD with pre-clinical models. It also aims to identify the specific links between brain regions, cell types and signalling pathways to behavioural endpoints related to motor and non-motor symptoms of PD.
MJFF believes that supporting fundamental investigations into the neural circuits and cellular targets that contribute to the presentation of motor and non-motor symptoms of PD will yield crucial insights needed to eventually develop better symptomatic therapeutics.
Funding will support projects that aim to:
- Characterise the emergence, time course, progression and severity of behavioural symptoms in animal models of PD.
- Identify and manipulate neural circuits whose activity underlies or modifies behavioural symptoms in animal models of PD.
- Identify cell types, neurotransmitter and neuromodulator receptors, or intracellular signalling pathways that are enriched in the brain regions and neural circuits contributing to behavioural symptoms in animal models of PD.
- Test pre-clinical therapeutic interventions to ameliorate behavioural symptoms in animal models of PD.
Projects will be supported that propose to use a variety of animal models of PD, including: mouse, rat and non-human primate systems; and genetic, toxin, lesion or protein aggregation-based models of PD.
When considering proposals submitted to this program, MJFF will prioritise those that:
- Focus on behavioural endpoints and tasks in animal models that are aligned with core motor and non-motor symptomatic domains representing unmet clinical needs in people with Parkinson’s.
- Focus on behavioural endpoints and tasks that may be translatable across species from rodent to non-human primate.
- Propose to study behavioural endpoints and tasks in balanced cohorts of male and female animals in a longitudinal design to monitor symptom emergence and severity over time.
- Propose to employ state-of-the-art methods to monitor neural circuit activity during behavioural task performance, such as high-density electrophysiological recording probes or genetically encoded calcium indicators to gain insights into the single-cell and population-level patterns of activity that associate with behavioural task performance.
- Propose to test the causal contribution of specific neural circuits, cell types or connections to behavioural symptom presentation in animal models of PD eg by using optogenetic, chemogenetic or electrical stimulation techniques.
- Seek to identify novel, potentially ‘druggable’ biological targets that are enriched in specific neural circuits shown to contribute to behavioural symptoms in animal models of PD, such as unique cell types, neuromodulator and neurotransmitter receptor combinations, ion channels and transporters, or intracellular signalling pathways.
- Propose to test the efficacy of translational therapeutic interventions to modify behavioural symptom expression, severity or duration in animal models of PD, including DBS-like circuit stimulation, optogenetic or chemogenetic circuit activation and inhibition, and pharmacological or gene therapies targeting biological pathways shown to be enriched within an identified circuit contributing to a specific symptom domain.
Industry and academic researchers based in any country are eligible to apply.