- Characterize the neurodevelopmental and neurodegenerative changes in FA affected tissues, and their implications for pathogenesis and therapies
- Discriminate the contribution and temporal cascade of cell dysfunction and cell loss in the pathology of affected tissues
- Elucidate the contribution of non cell-autonomous mechanisms to the pathophysiology of FA and as in relation to the development of effective treatments
RESEARCH PRIORITIES
FARA Grant Program Priorities
The FARA grant program supports basic, translational and clinical research with the goal of advancing therapeutic development in FA. All proposed research must fall within at least one of FARA’s Grant Program Priorities.
GRANT PRIORITY
Advancing understanding of neuroscience/systems
GRANT PRIORITY
Advancing understanding of cardiac disease in FA
- Characterize the molecular mechanisms, genetic factors, or biochemical pathways that determine heart health in FA, with a special emphasis on understanding the metabolism of the FA heart
- Comparisons of FA hearts to other genetic and non-genetic cardiomyopathies, with the goal of identifying common disrupted pathways responding to established treatments in other forms of cardiac disease
- Identification of biomarkers that are predictive of cardiac outcome or can be used in risk stratification of disease
- Develop therapies to reduce morbidity and mortality of the cardiac disease. This may include assessing currently approved therapeutic interventions as applied to FA
GRANT PRIORITY
Advancing understanding of the molecular basis of FA
- Identification of the precise mechanisms of GAA-mediated FXN gene silencing and physiological regulation of FXN expression as they relate to the identification of novel therapeutic targets
- Understand FeS cluster biogenesis and regulation in the context of frataxin deficiency
- Identification of other functions of frataxin
- Identification and characterization of disrupted pathways in FA cells/tissues, especially those targetable with small molecules
- Exploration of the molecular and metabolic basis of cell/tissue-type specific vulnerability
GRANT PRIORITY
Advancing drug discovery
- Develop FXN gene and protein replacement approaches, recognizing the limitation of unregulated gene expression and explore new tools for fine tuning transgene expression
- Investigate the application of novel gene editing tools to the FXN locus
- Exploration of approaches to increase frataxin by targeting epigenetic silencing, FXN transcription, translation and protein turnover, particularly discovery of site-specific epigenetic editors/transcriptional modulators
- Develop approaches that use small molecules to target well-validated disrupted pathways in FA, especially if synergistic with Nrf2 activation
- Discovery of strategies that can bypass frataxin function or rescue FeS biogenesis
GRANT PRIORITY
Facilitating the drug development process and translational research
- Studies to evaluate mechanism of action and target engagement, drug efficacy, safety and toxicity profiles in animals and identification of lead candidates
- Exploration of drug delivery systems for gene and protein therapy approaches, specifically novel viral and non-viral gene delivery systems
- Discovery and validation of biomarkers. Specifically, development of methods to measure frataxin in affected tissues and identification of novel pharmacodynamic markers to evaluate the response to therapeutics in affected inaccessible tissues, based on biochemical activities dependent on/downstream of frataxin function
- Investigate the application of new 3D cell models for in vitro tissue/organ disease modelling, aimed at supporting decision making in drug development
GRANT PRIORITY
Advancing clinical research
- Understand the natural history of FA, especially studies that utilize or expand resources of the FA Global Clinical Consortium
- Identification of early (including pre-symptomatic) quantifiable functional and clinical outcome measures for pediatric clinical trials
- Identification of novel, clinically meaningful, functional endpoints with measurable changes detectable within one year, especially those based on the use of digital and at-home monitoring devices
- Determine and validate quantitative tools reporting on functional clinical endpoints for the heart in FA, including development of new tools or approaches to accommodate the exercise limitations of FA patients
- Clinical and metabolic characterization of fatigue in FA
- Investigator-initiated clinical trials