My Career – Chapter 3: Friedreich’s Ataxia
Advancing Friedreich’s Ataxia Research
During my PhD at ULB (Université Libre de Bruxelles), I had the opportunity to collaborate with Professor Massimo Pandolfo’s team on a project addressing Friedreich’s ataxia (FRDA), a rare and debilitating neurodegenerative disorder. This collaboration unfolded alongside my doctoral research, requiring meticulous coordination and dedication to both endeavors. It represented a perfect intersection of my expertise in neuroscience and my desire to contribute to translational medical research.
Friedreich's ataxia (FA) is a rare, inherited disorder that causes progressive damage to the nervous system, leading to movement and sensory symptoms, as well as difficulties with walking and gait. In FA, nerve fibers in the spinal cord and peripheral nerves deteriorate, becoming thinner. The cerebellum, the part of the brain that coordinates balance and movement, is also affected. This degeneration results in motor weakness and sensory loss.
Developing a Cellular Model for FRDA
The project utilized patient-derived induced pluripotent stem cells (iPSCs) to generate neurons and cardiomyocytes—two cell types severely impacted in FRDA. These cells retained the hallmark GAA trinucleotide repeat expansion in the frataxin gene, reproducing the genetic underpinnings of the disease. My role in this work was central to developing and characterizing these neuron models, which revealed critical mitochondrial dysfunction—a key feature of FRDA pathology.
For the first time, we demonstrated decreased mitochondrial membrane potential in neurons and progressive mitochondrial degeneration in cardiomyocytes, providing a reliable platform for exploring FRDA’s underlying mechanisms. Our findings were published in Disease Models & Mechanisms (2013), in the article titled ‘Neurons and Cardiomyocytes Derived from Induced Pluripotent Stem Cells as a Model for Mitochondrial Defects in Friedreich’s Ataxia.’
Translating Science into Therapeutics
The cellular model we developed proved invaluable for drug discovery efforts. It was later used in screening studies that identified GLP-1 analogs, including exenatide, as potential therapeutic agents. This work demonstrated that exenatide could improve mitochondrial function and induce frataxin expression in patient-derived neurons and sensory cells. These findings informed a pilot clinical trial, marking a significant milestone in FRDA treatment research.
The therapeutic potential of our model and its role in clinical applications was highlighted in JCI Insight (2020), in the paper titled “Exenatide Induces Frataxin Expression and Improves Mitochondrial Function in Friedreich Ataxia.”
Bridging Fundamental Science and Patient Impact
This collaboration was particularly meaningful to me because it bridged fundamental neuroscience with translational medicine. It demonstrated how rigorous cellular modeling could directly inform clinical applications, offering hope for better treatments for patients. Moreover, it underscored the importance of interdisciplinary teamwork, as I worked closely with experts in molecular biology, stem cell research, and mitochondrial function.
Being part of a project that not only advanced scientific knowledge but also contributed to the development of therapeutic approaches reaffirmed my commitment to research with tangible societal impact. The ability to see my work contribute to a clinical trial was a deeply rewarding experience, emphasizing the value of connecting basic research with real-world applications.
Description
Friedreich’s Ataxia Research
Created an iPSC-derived neuronal model revealing mitochondrial dysfunction in Friedreich’s ataxia, directly contributing to clinical trials for therapeutic interventions.