2023-11-10 16:24:14
Indi Gregory’s disease, the small center of a legal case between Italy and Great Britain, was discovered in 2013 by researchers from the ‘Aldo Moro’ University of Bari in collaboration with an Israeli-Palestinian team. The Apulian university highlights the achievement achieved 10 years ago. The study relating to the pathology was published in the ‘Journal of Medical Genetics’.
The pathology from which the little girl suffers is called combined D,L-2-hydroxyglutaric aciduria and is a neuro-metabolic disease characterized by an accumulation in the urine of D-2-hydroxyglutarate and L-2-hydroxyglutarate, two mirror forms of a metabolite produced in the mitochondria.
This is a genetic pathology caused by mutations in the SLC25A1 gene, which contains the information to produce a protein, the mitochondrial citrate transporter, which in healthy people allows this important metabolic intermediate to escape from the mitochondria. The disease is transmitted by inheritance and is recessive, that is, it requires the transmission of two copies of the mutated gene from both parents: if both are healthy carriers of a mutation in the SLC25A1 gene, each child will have a 25% chance of being affected by the disease, 50% of being a healthy carrier and 25% of being healthy and not a carrier of the mutation.
Those with mutations in the SLC25A1 gene present different symptoms. In the most serious cases the disease is progressive and manifests itself with a form of severe encephalopathy with epileptic seizures from birth, respiratory failure which in the heaviest forms requires dependence on the ventilator, and malformations such as those which prevent the formation of the corpus callosum which connects the two hemispheres of the brain, described for the first time in the study signed by UniBa. In 2014 the same researchers, in collaboration with the Center for Neuromuscular Diseases of the University of Newcastle (UK), characterized for the first time a milder form associated with muscle weakness, particularly evident in both the arms and legs, but not lethal. Following these studies, to date approximately 50 patients have been identified worldwide with a variable clinical picture who, by combining molecular and clinical data in a retrospective study funded by Telethon and published in the ‘Journal of Inherited Metabolic Disease’ in 2018, researchers baresi have proposed to be associated with variable levels of citrate transporter activity.
The laboratory of Luigi Palmieri, full professor of Biochemistry and director of the Department of Biosciences, Biotechnology and Environment of the University of Bari – highlights the university – boasts over 30 years of experience in the study of mitochondrial transporters and associated pathologies.
Currently, for the majority of mitochondrial diseases there is no cure and for some serious mutations such as Indi there are no therapies available that can slow down the course of the disease. One hope is represented by the development of gene therapies. With this objective, Palmieri and colleagues are actively involved in the national research center ‘Development of gene therapy and drugs with RNA technology’, financed by the Pnrr, of which the University of Bari is one of the main nodes (Spoke).
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