Dr Rita Horvath  

Dr Rita Horvath is an academic neurologist and researcher specializing in rare neurogenetic disorders. She holds a professorship in Neurogenetics at the University of Cambridge's Department of Clinical Neurosciences, and serves as a Honorary Consultant at Addenbrooke's Hospital. 

Dr Horvath began her medical training in Budapest, Hungary, and pursued laboratory research at the Montreal Neurological Institute during her PhD focusing on mitochondrial diseases. She further honed her expertise in mitochondrial diagnostics and research during her tenure in Munich from 1999 to 2007. In 2007, she joined Newcastle University as a researcher in the Mitochondrial Research Group, establishing her own research team dedicated to mitochondrial translation deficiencies. 

In 2018, Professor Horvath took on a new position at the University of Cambridge's Department of Clinical Neurosciences, where in 2023 she has been appointed as Professor of Neurogenetics and a Fellow of the Academy of Medical Sciences. Her research primarily focuses on identifying the molecular bases of rare inherited neurological conditions, such as mitochondrial diseases and Charcot-Marie-Tooth disease, with the aim of developing effective treatments. She has been instrumental in applying genomics and biochemistry to diagnose these disorders, enabling precision genetic approaches for patient care. 

Throughout her career, Professor Horvath has established extensive international collaborations, extending her impact to benefit patients globally. Her commitment to developing new treatments for rare diseases has recently including pioneering novel therapy approaches for rare disorders. 

mT tRNA disorders, moving towards therapy

Mitochondrial diseases are clinically and genetically very heterogeneous, caused by mutations in the mitochondrial DNA (mtDNA) or in over 400 nuclear genes. They can affect multiple neurological systems, and also often involve other non-neurological organs and tissues.  Specific clinical syndromes have been associated with some mitochondrial diseases, but there is considerable phenotypic overlap with other neuromuscular and neurometabolic diseases. Therefore first-line exome and whole genome sequencing have become a cost-effective way of reaching a molecular diagnosis promptly in mitochondrial disease. Despite the significantly improved diagnostic yield, there are still no effective treatments for most patients with mitochondrial disease. 

Mitochondria play a central role in the homeostasis of cells, but mitochondrial insults preferentially affect some cell-types and not others. The reasons for this are not clear. The aim of our research is to define principal mechanisms underpinning cell-type-specific mitochondrial vulnerability in different organs and cell types. We use iPSC-derived neuronal models of mitochondrial disease including brain organoids to better understand this vulnerability in neurons. To study the effect of mitochondrial dysfunction in vivo, we applied CRISPR/Cas9 mutagenesis in zebrafish. The data obtained in neuronal cells and in zebrafish highlight some relevant molecular pathways which we study to develop treatments for mitochondrial disease. 

The presentation will highlight some of the therapy development for some rare forms of nuclear mitochondrial diseases, including the development of a clinical study in children with mitochondrial tRNA synthetase mutations.