MICROSATELLITE REPEAT EXPANSIONS
Over forty diseases, including Friedreich’s Ataxia and some genetic forms of neuromuscular disease and spinocerebellar ataxias, are driven by pathological expansion of DNA microsatellite repeats. Mechanisms by which microsatellite repeats drive disease are still emerging and may vary among diseases, but the clear molecular driver of disease is the length of the repeat in affected tissue. Accordingly, to some extent multiple diseases may have shared pathophysiology. Pfizer scientists are interested in establishing collaborations with expert partners in areas that would advance our understanding of microsatellite repeat expansions and our ability to intervene therapeutically to arrest or prevent pathological expansion and downstream consequences.
Pfizer is exploring partnering opportunities to expand our understanding of mechanisms that govern the length of DNA microsatellite repeats, and to identify potential therapeutic interventions and modalities.
Specific areas of interest include:
- Preclinical models of disease, cellular and animal
- Translational biomarkers specific to expanded repeat length in pathological context
- Identification and prosecution of small molecule targets that govern repeat length
- Approaches to gene editing and gene therapy for treatment of repeat expansion diseases
- Molecular mechanisms that govern microsatellite repeat pathology
- Novel methods for analysis of heterogeneity within repeat sequences and of repeat sequences genome-wide
- Therapeutic approaches to disease that target pathological mechanisms, including downstream to the disease-causing allele