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

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

doi:10.1186/s13023-019-1128-z

Cited by 23 publications

(16 citation statements)

References 43 publications

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“…F drial DNA (mtDNA) copy number, and the levels of the mitochondrial transcription factor A (TFAM) mRNA in HepG2 (see Glossary) cells. However, after reducing the glucose concentration, cells become more dependent on mitochondrial metabolism to obtain energy [3]. Thus, when glucose 25 mM was substituted by glucose-free/galactose 10 mM in the culture medium, HeLa and U2OS cells increased respiration and activities and levels of respiratory supercomplexes.…”

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confidence: 99%

Oxidative phosphorylation system and cell culture media

Bayona‐Bafaluy

Montoya

Ruiz‐Pesini

2021

Trends in Cell Biology

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confidence: 99%

Oxidative phosphorylation system and cell culture media

Bayona‐Bafaluy

Montoya

Ruiz‐Pesini

2021

Trends in Cell Biology

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“…There are also studies suggesting a potential beneficial effect of KD in MD, besides reducing seizures [ 14 , 18 ]. However, this was mainly studied in patient derived fibroblasts and animal models [ 8 , 14 , 19 – 23 ]. Of note, while it was previously assumed that the liver provides ketone bodies to the brain, astrocytes itself have shown to be ketogenic cells.…”

Section: Introductionmentioning

confidence: 99%

Ketogenic diet for mitochondrial disease: a systematic review on efficacy and safety

Zweers

Wegberg

Janssen

et al. 2021

Orphanet J Rare Dis

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Background No curative therapy for mitochondrial disease (MD) exists, prioritizing supportive treatment for symptom relief. In animal and cell models ketones decrease oxidative stress, increase antioxidants and scavenge free radicals, putting ketogenic diets (KDs) on the list of management options for MD. Furthermore, KDs are well-known, safe and effective treatments for epilepsy, a frequent symptom of MD. This systematic review evaluates efficacy and safety of KD for MD. Methods We searched Pubmed, Cochrane, Embase and Cinahl (November 2020) with search terms linked to MD and KD. From the identified records, we excluded studies on Pyruvate Dehydrogenase Complex deficiency. From these eligible reports, cases without a genetically confirmed diagnosis and cases without sufficient data on KD and clinical course were excluded. The remaining studies were included in the qualitative analysis. Results Only 20 cases (14 pediatric) from the 694 papers identified met the inclusion criteria (one controlled trial (n = 5), 15 case reports). KD led to seizure control in 7 out of 8 cases and improved muscular symptoms in 3 of 10 individuals. In 4 of 20 cases KD reversed the clinical phenotype (e.g. cardiomyopathy, movement disorder). In 5 adults with mitochondrial DNA deletion(s) related myopathy rhabdomyolysis led to cessation of KD. Three individuals with POLG mutations died while being on KD, however, their survival was not different compared to individuals with POLG mutations without KD. Conclusion Data on efficacy and safety of KD for MD is too scarce for general recommendations. KD should be considered in individuals with MD and therapy refractory epilepsy, while KD is contraindicated in mitochondrial DNA deletion(s) related myopathy. When considering KD for MD the high rate of adverse effects should be taken into account, but also spectacular improvements in individual cases. KD is a highly individual management option in this fragile patient group and requires an experienced team. To increase knowledge on this—individually—promising management option more (prospective) studies using adequate outcome measures are crucial.

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“…Nutritional interventions are thought to have the potential to enhance mitochondrial bioenergetic capacity. Ketogenic diet (high in fat and low in carbohydrates) mimics the state of ketosis induced by starvation and is thought to have a neuroprotective effect by increasing antioxidant capacity ( 55 , 56 ).…”

Section: Medical Treatmentmentioning

confidence: 99%

Leber Hereditary Optic Neuropathy: Review of Treatment and Management

Hage

Vignal-Clermont

2021

Front. Neurol.

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Leber hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disease that specifically targets the retinal ganglion cells by reducing their ability to produce enough energy to sustain. The mutations of the mitochondrial DNA that cause LHON are silent until an unknown trigger causes bilateral central visual scotoma. After the onset of loss of vision, most patients experience progressive worsening within the following months. Few of them regain some vision after a period of ~1 year. Management of LHON patients has been focused on understanding the triggers of the disease and its pathophysiology to prevent the onset of visual loss in a carrier. Medical treatment is recommended once visual loss has started in at least one eye. Research evaluated drugs that are thought to be able to restore the mitochondrial electron transport chain of the retinal ganglion cells. Significant advances were made in evaluating free radical cell scavengers and gene therapy as potential treatments for LHON. Although encouraging the results of clinical trial have been mixed in stopping the worsening of visual loss. In patients with chronic disease of over 1 year, efficient treatment that restores vision is yet to be discovered. In this review, we summarize the management strategies for patients with LHON before, during, and after the loss of vision, explain the rationale and effectiveness of previous and current treatments, and report findings about emerging treatments.

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

Cited by 23 publications

References 43 publications

Oxidative phosphorylation system and cell culture media

Oxidative phosphorylation system and cell culture media

Ketogenic diet for mitochondrial disease: a systematic review on efficacy and safety

Leber Hereditary Optic Neuropathy: Review of Treatment and Management

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