Research Grant Award

Friedreich's Ataxia Special Projects Award

Dr. Brigitte Sturm

Medical University of Vienna, Austria
The role of frataxin in heme-synthesis

Friedreich's ataxia (FRDA) is a severe genetic disorder affecting approximately one in 50,000 people. The most common FRDA symptoms include muscle weakness and loss of coordination, vision impairment, hearing loss, heart muscle abnormalities, scoliosis, and diabetes. The underlying cause of FRDA is a mutation in the FRDA gene which results in reduced levels of an essential protein named frataxin in all cells of the body. The function of frataxin is still unclear but there is some evidence that frataxin plays a role in heme synthesis (the production of hemoglobin which consists of heme and globin proteins and is essential for oxygen transport in the body).

In this study we will investigate the role of frataxin in heme synthesis. For this study we will use cells from a FRDA humanized mouse model which contains the entire human gene frataxin instead of the mouse gene for frataxin. These mice manifest the main symptoms of FRDA as found in patients. We will collect progenitor cells from these mice and from blood from FRDA patients and will turn them into red blood cells under laboratory- controlled conditions. Progenitor cells refer to immature or undifferentiated cells and share many common features with stem cells.

Progenitor cells have a capacity for self-renewal and differentiation and can switch during the differentiation process into red blood cells. During differentiation high levels of heme are synthesized. Therefore it will provide us a very good tool to study a possible influence of frataxin on heme-synthesis under conditions which mimic the situation in the body. Using an optimal model for studying heme synthesis this project will enable us to characterise the role of frataxin during heme synthesis.