Monitoring clinical progression with mitochondrial disease biomarkers

Horvath, Rita; Lyon, Jon; Chinnery, Patrick F.

doi:10.1093/brain/awx168

Cited by 47 publications

(55 citation statements)

References 127 publications

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“…The development of mitochondrial therapies for common diseases faces considerable challenges. A key issue is the difficulty in assessing mitochondrial function and damage noninvasively in patients 253 . Currently, it can be difficult to know when to treat a patient with a mitochondrial therapy, or to determine whether the putative therapy acts on mitochondria or elsewhere 253 .…”

Section: Challengesmentioning

confidence: 99%

“…A key issue is the difficulty in assessing mitochondrial function and damage noninvasively in patients 253 . Currently, it can be difficult to know when to treat a patient with a mitochondrial therapy, or to determine whether the putative therapy acts on mitochondria or elsewhere 253 . There is an urgent need for biomarkers that are specific, sensitive over short periods of time and clinically meaningful 253 .…”

Section: Challengesmentioning

confidence: 99%

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Mitochondria as a therapeutic target for common pathologies

Murphy

Hartley

2018

Nat Rev Drug Discov

582

419

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Although the development of mitochondrial therapies has largely focused on diseases caused by mutations in mitochondrial DNA or in nuclear genes encoding mitochondrial proteins, it has emerged that mitochondrial dysfunction also contributes to the pathology of many common disorders, including neurodegeneration, metabolic disease, heart failure, ischaemia-reperfusion injury and protozoal infections. Mitochondria therefore represent an important drug target for these highly prevalent diseases. Several strategies aimed at therapeutically restoring mitochondrial function are emerging and a small number of agents have entered clinical trials. This review will discuss the opportunities and challenges faced for the further development of a mitochondrial pharmacology for common pathologies.

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Section: Challengesmentioning

confidence: 99%

Section: Challengesmentioning

confidence: 99%

Mitochondria as a therapeutic target for common pathologies

Murphy

Hartley

2018

Nat Rev Drug Discov

582

419

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“…These include protein replacement; small molecules including antioxidants, amino acids and nucleotide supplementation; cell therapy; and gene manipulation (Nightingale et al, 2016). Although pre-clinical studies have seen the greatest progress, several are now under evaluation in clinical trials (Steele et al, 2017). One approach is to induce mitochondrial biogenesis, which is effective in animal models of mitochondrial diseases (Ahola-Erkkila et al, 2010;Viscomi et al, 2011;Cerutti et al, 2014;Peralta et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Metabolic effects of bezafibrate in mitochondrial disease

et al. 2020

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Mitochondrial disorders affect 1/5,000 and have no cure. Inducing mitochondrial biogenesis with bezafibrate improves mitochondrial function in animal models, but there are no comparable human studies. We performed an open‐label observational experimental medicine study of six patients with mitochondrial myopathy caused by the m.3243A>G MTTL1 mutation. Our primary aim was to determine the effects of bezafibrate on mitochondrial metabolism, whilst providing preliminary evidence of safety and efficacy using biomarkers. The participants received 600–1,200 mg bezafibrate daily for 12 weeks. There were no clinically significant adverse events, and liver function was not affected. We detected a reduction in the number of complex IV‐immunodeficient muscle fibres and improved cardiac function. However, this was accompanied by an increase in serum biomarkers of mitochondrial disease, including fibroblast growth factor 21 (FGF‐21), growth and differentiation factor 15 (GDF‐15), plus dysregulation of fatty acid and amino acid metabolism. Thus, although potentially beneficial in short term, inducing mitochondrial biogenesis with bezafibrate altered the metabolomic signature of mitochondrial disease, raising concerns about long‐term sequelae.

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“…La CPEO se caracteriza por ptosis palpebral, alteración de los movimientos oculares con pupilas normales y, en algunos casos, cursa con afectación de la musculatura facial (12)(13) . Puede asociarse con un compromiso multisistémico con la afectación de la retina, el cerebelo, el corazón y los músculos laríngeos (13)(14)(15) . Nuestro paciente presentaba trastorno grave de la deglución con aspiraciones silentes y la alteración de la voz, consistente en baja tonalidad y disfonía.…”

Section: Discussionunclassified

Neumopatía crónica secundaria al trastorno de la deglución en un paciente con miopatía mitocondrial

Palacio-Petri

Morales-Múnera

Ortiz

2019

Iatreia

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Introducción: la enfermedad pulmonar crónica secundaria a la disfagia es una complicación frecuente en los pacientes con enfermedades neuromusculares. Las miopatías mitocondriales son un conjunto de enfermedades que pueden conducir a daño pulmonar progresivo, secundario al síndrome aspirativo crónico.Caso clínico: niño de 7 años con signos clínicos y radiológicos de enfermedad pulmonar crónica; además, con desnutrición crónica, debilidad muscular, disfonía y oculoparesia externa crónica multiplanar. Su padre tuvo síntomas similares desde la infancia y requirió alimentación con dieta espesa por trastorno de la deglución. Se confirma en el paciente la presencia de disfagia como la causa de la neumopatía crónica y se sospecha miopatía congénita hereditaria. En consecuencia, se realiza el diagnóstico de enfermedad mitocondrial con oculoparesia externa crónica, mediante la secuenciación del gen polimerasa gamma del ADN mitocondrial (POLG).Conclusiones: en los pacientes con neumopatía crónica se deben considerar las enfermedades neuromusculares en el diagnóstico diferencial. La miopatía mitocondrial con oculoparesia externa crónica progresiva, se asocia con trastorno de la deglución hasta en un 50 % de los casos. El diagnóstico temprano es importante para retardar el deterioro de la función pulmonar.

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Monitoring clinical progression with mitochondrial disease biomarkers

Cited by 47 publications

References 127 publications

Mitochondria as a therapeutic target for common pathologies

Mitochondria as a therapeutic target for common pathologies

Metabolic effects of bezafibrate in mitochondrial disease

Neumopatía crónica secundaria al trastorno de la deglución en un paciente con miopatía mitocondrial

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