In this project, Dr Aquilano and her group aim to investigate a previously unexplored potential contributor to disease progression in FA: extracellular traps (ETs). ETs are web-like structures composed of DNA and proteins that are typically released by immune cells in response to stress or infection. While their primary function is to trap and neutralize pathogens, emerging evidence suggests that in several human diseases, including neurological diseases, these structures may instead be driving harmful inflammation.
Dr Aquilano’s previous studies have shown that both microglia (the brain’s resident immune cells) and adipocytes (fat cells) become abnormally activated in the absence of frataxin, adopting a pro-inflammatory state. Preliminary data from her laboratory also shows increased expression of ET-related genes in FA mouse models. She now hypothesizes that frataxin-deficient cells may release ET-like structures, which could amplify chronic inflammation, thereby worsening neurological symptoms and contributing to metabolic complications such as insulin resistance.
This will be the first study to directly assess whether ETs are formed in FA and to evaluate their potential role in disease progression. Dr Aquilano’s lab will analyze microglia and adipocytes derived from established FA models to determine whether ETs are produced, what they consist of, and how they affect nearby neurons and metabolic functions. Her lab will test existing pharmacological inhibitors known to block ET formation. If these compounds are effective in reducing the release or toxicity of ETs, they could represent a novel class of anti-inflammatory therapies for FA, complementing current treatment approaches by targeting a previously unrecognized mechanism.