Repeat Expansion

Over fifty diseases, most of which primarily affect the nervous system, are caused by expansion of short DNA sequence repeats dispersed throughout the genome. Mechanisms by which expanded repeats drive disease are still emerging and may vary among diseases. However, somatic expansion of repeats in affected tissues appears to be a common pathological driver. Pfizer scientists are interested in establishing collaborations with expert partners in areas that would advance our understanding of mechanisms of DNA repeat expansion 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 repeats, and to identify potential therapeutic interventions and modalities.

Specific areas of interest include:

• Novel targets that directly impact the pathogenic repeats
• Molecular mechanisms that modulate pathological repeat length, repeat transcription or translation, or toxic gain-of-function of repeat transcripts
• Biochemical and cell-based assays for DNA mismatch repair or repeat instability
• Translational biomarkers of somatic repeat instability
• Preclinical models of disease, cellular and animal
• Molecular mechanisms that govern microsatellite repeat pathology

Disease areas of high interest include but are not limited to Huntington’s disease (HD), myotonic dystrophy (DM1), Friedreich’s ataxia (FRDA), C9orf72 amyotrophic lateral sclerosis (ALS)