The National Ataxia Foundation (NAF) has presented a researcher from Belgium, Simona Donatello, with its Young Investigator Research Award for her work on molecular mTOR pathways affecting frataxin expression in Friedreich’s ataxia, possibly unearthing novel drug targets for the treatment of the disease.
Dr. Donatello, with the Universite Libre de Bruxelles, aims to investigate the role of a protein called the mechanistic Target Of Rapamycin (mTOR) in disease mechanisms brought on by the mutated frataxin mitochondrial protein — the underlying cause of Friedreich’s ataxia.
mTOR is known to control numerous key cellular processes such as cell growth, multiplication, survival, and motility, as well as protein transcription and translation. The factor is also known to integrate metabolic pathways, and in recent years has been investigated as a potential drug target in diseases as disparate as cancer and depression.
While scientists debate potential mechanisms linking the protein to frataxin function, no systematic study of mTOR’s involvement in Friedreich’s ataxia has been performed to date. Studies indicate that mTOR might have contrasting roles in neurons and glial cells called astrocytes in the central nervous system.
Dr. Donatello believes a deeper understanding of how mTOR interacts with frataxin might reveal new drug targets in Friedreich’s ataxia.
Her project will employ a model using induced pluripotent stem cells derived from skin cells called fibroblasts. These cells will be isolated from both patients and healthy individuals serving as controls, and once the stem cells are produced, they will be further developed into neurons and glial cells. This model will allow Dr. Donatello to manipulate mTOR and frataxin expression to further understanding of how the two proteins interact.
The in vitro approach will also enable her to study the differences in interactions imposed by the various cellular localizations, and how mTOR signaling in different cells might impact the disease.
Using a known blocker of mTOR — rapamycin — Dr. Donatello will explore treatment approaches that might alter the expression and cellular oxidation of the mutant frataxin protein.