Two winners / AAP AMMi and FMR

October 13, 2021 | News

The Foundation For Rare Diseases and the association AMMi have jointly launched a call for projects on the MTFMT gene and Leigh syndrome. Two projects have been selected for funding among the winning projects.

Mitochondrial diseases are muscular and neurodegenerative disorders caused by mutations in nuclear (nDNA) or mitochondrial (mtDNA) DNA, most of which have no effective treatment. One of the most serious clinical manifestations of mitochondrial diseases is Leigh syndrome (LS). This syndrome is a severe, progressive neurological disease characterized by necrotizing lesions in the brain. It is caused by variants in many genes, including MTFMT. MTFMT encodes the methionyl-tRNA formyltransferase mt, which is required for efficient initiation of mtRNA translation. Indeed, variants and deletion of MTFMT affect the synthesis of the subunits of the respiratory complexes encoded by mt, as well as the assembly of each complex and super-complexes, resulting in a decrease in oxidative phosphorylation.

- Dr. Lenaers' team (Angers - France) proposes to test on fibroblasts from patients with bi-allelic variants in MTFMT, three different approaches, each with a sufficiently strong rationale to hypothesize that they can, through different pathways, improve mitochondrial physiology, possibly in a complementary manner. The three compounds will be tested individually or in combination, on mitochondrial physiology.

- The team of Prof. Prigione (Düsseldorf - Germany) proposes to evaluate the therapeutic efficacy of other available treatments in induced neurons derived from patients with MTFMT mutations and to study the effects of these treatments on the pathophysiological alterations present in the mutant cells.