Final Report Summary - RNA DISEASES (UNDERSTANDING THE CAUSES OF THE RNA GAIN OF FUNCTION DISEASES)
The goal of this ERC funding (“RNA disease”) was to understand how mutation located in the “non-coding” part of the genome could lead to human inherited diseases. We focused our studies on neuromuscular and neurodegenerative genetic disorders, notably on Myotonic Dystrophy (DM), which are the most common muscular dystrophy in adults; on the neurodegenerative Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS); on the most common genetic cause of Amyotrophic Lateral Sclerosis associated to Frontotemporal Dementia (ALS-FTD) and on the rare Spinocerebellar Ataxia 10 and 31 (SCA10 and SCA31). Our project was to identify the molecular mechanisms explaining how these expanded repeats are pathogenic.
Briefly, we found that alteration of the cardiac sodium channel SCN5A may explain the cardiac conduction and arrhythmia observed in patients with Myotonic Dystrophy (DM, also named Steinert disease). Furthermore, we uncovered the molecular cause of FXTAS and developed novel cell and animal models for this neurodegenerative disease. Finally, we clarified the molecular and cellular functions of the C9ORF72 protein involved in Amyotrophic Lateral Sclerosis (ALS), which we found involved in autophagy, a protein degradation mechanism essential to neuron viability. These keys advances will hopefully help to develop innovative therapeutic strategies for these devastating and currently incurable diseases.
Briefly, we found that alteration of the cardiac sodium channel SCN5A may explain the cardiac conduction and arrhythmia observed in patients with Myotonic Dystrophy (DM, also named Steinert disease). Furthermore, we uncovered the molecular cause of FXTAS and developed novel cell and animal models for this neurodegenerative disease. Finally, we clarified the molecular and cellular functions of the C9ORF72 protein involved in Amyotrophic Lateral Sclerosis (ALS), which we found involved in autophagy, a protein degradation mechanism essential to neuron viability. These keys advances will hopefully help to develop innovative therapeutic strategies for these devastating and currently incurable diseases.