Ketogenic treatment reduces the percentage of a LHON heteroplasmic mutation and increases mtDNA amount of a LHON homoplasmic mutation

Sonia Emperador,M Pilar Bayona-Bafaluy,Eduardo Ruiz-Pesini,Julio Montoya,Mouna Habbane,Ester López-Gallardo,Carmen Hernández-Ainsa

doi:10.1186/s13023-019-1128-z

Abstract

BackgroundThe vision loss in Leber hereditary optic neuropathy patients is due to mitochondrial DNA mutations. No treatment has shown a clear-cut benefit on a clinically meaningful end-point. However, clinical evidences suggest two therapeutic approaches: the reduction of the mutation load in heteroplasmic patients or the elevation of mitochondrial DNA amount in homoplasmic patients.ResultsHere we show that ketogenic treatment, in cybrid cell lines, reduces the percentage of the m.13094 T > C heteroplasmic mutation and also increases the mitochondrial DNA levels of the m.11778G > A mitochondrial genotype.ConclusionsThese results suggest that ketogenic diet could be a therapeutic strategy for Leber hereditary optic neuropathy.

Highlights

The vision loss in Leber hereditary optic neuropathy patients is due to mitochondrial DNA mutations
Leber hereditary optic neuropathy (LHON) is a kind of blindness due to retinal ganglion cells (RGC) loss provoked by pathologic mutations in the mitochondrial DNA, mainly in genes for respiratory complex I (CI) subunits
Reducing the heteroplasmic mutation percentage In a previous work, we described a LHON patient with the m

Summary

Introduction

The vision loss in Leber hereditary optic neuropathy patients is due to mitochondrial DNA mutations. Leber hereditary optic neuropathy (LHON) is a kind of blindness due to retinal ganglion cells (RGC) loss provoked by pathologic mutations in the mitochondrial DNA (mtDNA), mainly in genes for respiratory complex I (CI) subunits. Three of these mutations, m.3460G > A, m.11778G > A and m.14484. The lower the percentage of pathological mutation, the higher the probability of spontaneous recovery [4].

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Conclusion