Friedreich’s ataxia (FA) is caused by reduced levels of the protein frataxin and leads to progressive damage to the nervous system. While much research has focused on the effects of frataxin deficiency in nerve cells, growing evidence suggests that microglia, the immune cells of the brain, may also play an important role in disease progression. Recent studies have found that microglia in FA become abnormally activated, leading to inflammation, cellular stress, and damage that may contribute to neurodegeneration.
This project will investigate why microglia become hyperactive in FA and how dysfunction in key cellular compartments, including mitochondria and lysosomes, contributes to this process. Using stem cell-derived microglia from individuals with FA and a specialized mouse model containing human microglia, researchers will examine the mechanisms driving microglial dysfunction and test strategies designed to restore normal cellular function.
The goal is to determine whether improving the health and function of microglia can reduce harmful inflammation and better support the survival of nerve cells. This work could identify a new therapeutic approach for FA by targeting brain immune cells and may open new avenues for slowing neurodegeneration in people living with the disease.