A new lead in the treatment of MELAS syndrome

The MELAS syndrome is a mitochondrial disease with a partly neuromuscular expression and is related, in the vast majority of cases, to a point mutationModification soudaine et transmissible du matériel génétique. Elle peut être spontanée ou induite par des agents dits » mutagènes » (radiations, produits toxiques,…). (m.3243A>G) of the mitochondrial DNAmacromolécule complexe, l’ADN est le support de l’hérédité (gènes). C’est le constituant des chromosomes. L’ADN est organisé en double hélice (deux brins complémentaires) et constitué de nucléotides de quatre types : adénine, guanine, cytosine et thymine.. French specialists report laboratory work on a cellular model of the disease (cybrid cells with different levels of heteroplasmy of this mutant).

• A multi-omics approach was applied to this model.
• Glutamate concentration was found to be highly correlated with the level of heteroplasmy.
• Transcriptomic analysis revealed perturbations of other metabolic pathways such as gamma-amino-butyric acid and tricarboxylic acid.
• These results were confirmed by an autopsy study on a patient’s brain.
• The model cells subjected to a diet rich in ketones saw their glutamate levels drop, opening the way to possible therapeutic developments.

Glutamate-Induced Deregulation of Krebs Cycle in Mitochondrial Encephalopathy Lactic Acidosis Syndrome Stroke-Like Episodes (MELAS) Syndrome Is Alleviated by Ketone Body Exposure. Belal S, Goudenège D, Bocca C et al. Biomedicines. 2022 Jul 11;10(7):1665.