No approved-drug candidate for multiple mitochondrial dysfunctions syndrome 6 is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
No abstract in this set mentions multiple mitochondrial dysfunctions syndrome 6. The abstracts cover general mitochondrial disease management, diabetic retinopathy, primary CoQ deficiency, and neurodegenerative disease. A 2020 review states that mitochondrial diseases lack a specific disease-modifying therapy and patients are managed with supportive and symptomatic care. A 2025 review on mitochondrial myopathies confirms that no particular treatment exists and that available guidelines rest on expert opinion; the most common regimens use vitamins and cofactors but hard evidence of benefit is still lacking. A 2010 review of mitochondrial dysfunction in neurodegeneration notes that mitochondrially-targeted therapeutics that have reached clinical trials have produced encouraging but largely inconclusive results.
A 2015 phase IIa trial in non-proliferative diabetic retinopathy tested ubiquinone and combined antioxidant therapy in 60 patients. Baseline submitochondrial membrane fluidity was significantly diminished in all groups (placebo 0.14 ± 0.01 Ie/Im, ubiquinone 0.14 ± 0.01 Ie/Im, combined therapy 0.13 ± 0.00 Ie/Im) versus normal values (0.24 ± 0.01 Ie/Im). After treatment, fluidity increased significantly in the ubiquinone group (0.22 ± 0.01 Ie/Im) and combined therapy group (0.19 ± 0.01 Ie/Im), with no change in placebo. Hydrolytic activity of F0F1-ATPase, elevated at baseline, decreased significantly after ubiquinone (from 312.41 ± 25.63 to 213.25 ± 14.19 nmol PO4) and combined therapy (from 371.28 ± 33.50 to 225.55 ± 14.48 nmol PO4). A 2025 study in primary CoQ deficiency tested CoQ10 plus vanillic acid in Coq9R239X mice and human COQ7-deficient fibroblasts. Co-administration extended lifespan and improved motor function beyond either compound alone, reduced DMQ accumulation in kidney and liver, and showed anti-neuroinflammatory effects with reduced gliosis. The authors state that CoQ10 supplementation alone has limited efficacy due to poor bioavailability and restricted tissue distribution, especially to the central nervous system.
What is still missing for multiple mitochondrial dysfunctions syndrome 6 specifically: no clinical trial data, no patient-level evidence, no validated biomarkers for this genotype, and no funding directed at this ultra-rare condition. The combination strategy reported for primary CoQ deficiency has not been tested in any form of multiple mitochondrial dysfunctions syndrome. Patient stratification by genetic subtype and tissue-specific drug delivery remain unaddressed.
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Expert Opinion on Therapeutic Targets · 2010 · 82 citations
Targeting mitochondrial dysfunction in neurodegenerative disease: Part II
AbstractIMPORTANCE OF THE FIELD: With improvements in life expectancy over the past decades, the incidence of neurodegenerative disease has dramatically increased and new therapeutic strategies are urgently needed. One possible approach is to target mitochondrial dysfunction, which has been implicated in the pathogenesis of numerous neurodegenerative disorders. AREAS COVERED IN THIS REVIEW: This review examines the role of mitochondrial dysfunction in neurodegeneration, drawing examples from common diseases such as Alzheimer's disease and rarer familial disorders such as Charcot-Marie-Tooth. The review is provided in two parts. In part I we discussed the mitochondrial defects which have been most extensively researched (oxidative stress, bioenergetic dysfunction, calcium mishandling). We focus now on those defects which have more recently been implicated in neurodegeneration; in mitochondrial fusion/fission, protein import, protein quality control, kinase signalling and opening of the permeability transition pore. WHAT THE READER WILL GAIN: An examination of mitochondrial defects observed in neurodegeneration, and existing and possible future therapies to target these defects. TAKE HOME MESSAGE: The mitochondrially-targeted therapeutics that have reached clinical trials so far have produced encouraging but largely inconclusive results. Increasing understanding of mitochondrial dysfunction has, however, led to preclinical work focusing on novel approaches, which has generated exciting preliminary data.
https://doi.org/10.1517/14728221003730434Redox Report · 2015 · 23 citations · open access
The antioxidant effect of ubiquinone and combined therapy on mitochondrial function in blood cells in non-proliferative diabetic retinopathy: A randomized, double-blind, phase IIa, placebo-controlled study
AbstractOBJECTIVES: To evaluate the effect of ubiquinone and combined antioxidant therapy on mitochondrial function in non-proliferative diabetic retinopathy (NPDR) in a randomized, double-blind, phase IIa, placebo-controlled, clinical trial. Three groups of 20 patients were formed: Group 1, ubiquinone; Group 2, combined therapy; and Group 3, placebo (one daily dose for 6 months). METHODS: Fluidity of the submitochondrial membrane in platelets was determined by examining intensity of fluorescence between the monomer (Im) and excimer (Ie). Hydrolytic activity of the mitochondrial F0F1-ATPase was evaluated with the spectrophotometric method. RESULTS: Normal, baseline submitochondrial membrane fluidity, 0.24 ± 0.01 Ie/Im, was significantly diminished in the three study groups vs. normal values (P < 0.0001); placebo, 0.14 ± 0.01 Ie/Im; ubiquinone, 0.14 ± 0.01 Ie/Im; and combined therapy, 0.13 ± 0.00 Ie/Im. Afterward, it increased significantly (P < 0.0001), the ubiquinone group 0.22 ± 0.01 Ie/Im, combined therapy group, 0.19 ± 0.01 Ie/Im; with no changes the placebo group. Baseline hydrolytic activity of the F0F1-ATPase enzyme increased in the three study groups vs. normal values (184.50 ± 7.84 nmol PO4), placebo, 304.12 ± 22.83 nmol PO4 (P < 0.002); ubiquinone, 312.41 ± 25.63 nmol PO4 (P < 0.009); and combined therapy, 371.28 ± 33.50 nmol PO4 (P < 0.002). Afterward, a significant decrease the enzymatic activity: ubiquinone, 213.25 ± 14.19 nmol PO4 (P < 0.001); and combined therapy, 225.55 ± 14.48 nmol PO4 (P < 0.0001). DISCUSSION: Mitochondrial dysfunction significantly improved in groups of NPDR patients treated with antioxidants.
https://doi.org/10.1179/1351000215y.0000000032Journal of Clinical Medicine · 2020 · 14 citations · open access
Therapeutical Management and Drug Safety in Mitochondrial Diseases—Update 2020
AbstractMitochondrial diseases (MDs) are a group of genetic disorders that may manifest with vast clinical heterogeneity in childhood or adulthood. These diseases are characterized by dysfunctional mitochondria and oxidative phosphorylation deficiency. Patients are usually treated with supportive and symptomatic therapies due to the absence of a specific disease-modifying therapy. Management of patients with MDs is based on different therapeutical strategies, particularly the early treatment of organ-specific complications and the avoidance of catabolic stressors or toxic medication. In this review, we discuss the therapeutic management of MDs, supported by a revision of the literature, and provide an overview of the drugs that should be either avoided or carefully used both for the specific treatment of MDs and for the management of comorbidities these subjects may manifest. We finally discuss the latest therapies approved for the management of MDs and some ongoing clinical trials.
https://doi.org/10.3390/jcm10010094International Journal of Molecular Sciences · 2025 · 3 citations · open access
Advances in Management of Mitochondrial Myopathies
AbstractMitochondria, the energy factories of human organisms, can be the cause of a variety of genetic disorders called mitochondrial myopathies. Mitochondrial diseases arise from genetic alterations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) and can manifest with great heterogeneity, leading to multiorgan dysfunction. The purpose of this article is to concisely review the pathophysiology, genetics and main clinical features of mitochondrial myopathies, focusing mainly on the treatment and management of these disorders. Currently, a particular treatment for mitochondrial myopathies does not exist, while the available guidelines concerning management are based on experts' opinions. The therapeutic options currently applied largely aim at symptom relief and amelioration of patients' quality of life. The most commonly used regimens involve the administration of vitamins and cofactors, although hard evidence regarding their true benefit for patients is still lacking. Recent studies have demonstrated promising results for elamipretide; however, phase III clinical trials are still ongoing. Regarding patient management, a multidisciplinary approach with the collaboration of different specialties is required. Further clinical trials for the already applied treatment options, as well as on novel experimental therapies, are of utmost importance in order to improve patients' outcomes.
https://doi.org/10.3390/ijms26115411Translational Science of Rare Diseases · 2017 · 1 citations · open access
Meeting report from the Mitochondrial Medicine Southeast Regional Symposium — understanding mitochondrial disease and mitochondrial dysfunction: Opportunities and impacts in the clinic and laboratory
AbstractOn April 7th, 2017, the Foundation for Mitochondrial Medicine and the United Mitochondrial Disease Foundation held a Southeast Regional Symposium in Birmingham, Alabama to explore mitochondrial dysfunction, diseases and conditions related to mitochondrial dysfunction, their clinical management, and new therapies and tools to address those conditions. This article provides a report of the proceedings.
https://doi.org/10.3233/trd-170014Communications Medicine · 2025 · 1 citations · open access
The treatment of primary CoQ deficiency requires the targeting of multiple pathogenic mechanisms
AbstractPrimary coenzyme Q (CoQ) deficiency is a severe mitochondrial disorder characterized by diverse clinical manifestations due to multiple pathomechanisms. Although CoQ10 supplementation remains the standard treatment, its therapeutic efficacy is limited by poor bioavailability and restricted tissue distribution, especially to the central nervous system. In this study, we investigated the therapeutic potential of combining CoQ10 with vanillic acid (VA), a structural analog of 4-hydroxybenzoic acid, in both murine and human models of primary CoQ deficiency, through phenotypic, biochemical, and molecular analyses. In Coq9R239X mice, we demonstrate that co-administration of CoQ10 and VA significantly extends lifespan and improves motor function beyond the effects observed with either compound alone. Mechanistically, this enhanced therapeutic efficacy results from the complementary actions of both compounds, i.e., CoQ10 increases quinone pools in peripheral tissues and modulates one-carbon metabolism, particularly in the liver, while VA reduces DMQ accumulation in the kidney and liver and exhibits potent anti-neuroinflammatory properties, leading to a reduction in gliosis. The co-treatment shows remarkable tissue-specific responses, with the liver displaying the most pronounced metabolic adaptations. In this tissue, the combined therapy restores the expression of genes involved in sulfide oxidation and one-carbon metabolism pathways. We further validate these findings in human COQ7-deficient fibroblasts, where the co-treatment normalizes key metabolic pathways more effectively than individual treatments. Our findings demonstrate that combining CoQ10 with VA effectively addresses multiple pathogenic mechanisms in CoQ deficiency, resulting in enhanced therapeutic outcomes. This therapeutic strategy could represent a more effective and feasible treatment approach for mitochondrial disorders, particularly those involving CoQ deficiency and neurological manifestations. González-García et al. investigate the therapeutic potential of CoQ10 and vanillic acid supplementation in models of mitochondrial CoQ10 deficiency. The findings reveal synergistic benefits, including extended lifespan, improved mitochondrial function, and reduced neuroinflammation, highlighting vanillic acid’s potential to enhance CoQ10 efficacy. Mitochondrial diseases affect how cells produce energy, often leading to serious symptoms. One such condition, primary coenzyme Q (CoQ) deficiency, is usually treated with oral CoQ10, but these often don’t work well, especially for brain symptoms. In this study, researchers tested a new approach using a combination of CoQ10 and a natural compound called vanillic acid (VA). In both mice and human cells, this combined treatment worked better than either alone. It improved survival, energy production, and reduced brain inflammation. These findings may help improve future treatments for mitochondrial diseases.
https://doi.org/10.1038/s43856-025-01000-8Drug Development Research · 1999 · 0 citations
Mitochondria: Aspects for neuroprotection
AbstractThe understanding of mitochondrial biology and, subsquently, the role of mitochondrial pathology in human disease has increased exponentially over the past 30 years. As insight has increased, so attention has begun to shift to the possibilities for treating mitochondrially based disorders. There are a number of archetypal mitochondrial diseases, each associated with specific mitochondrial DNA mutations, deletions, or depletions. In addition there are a number of disorders, mainly neurodegenerative in nature, in which mitochondrial dysfunction appears to play a pivotal role. Mitochondrial structure and function are discussed. Treatment of the archetypal mitochondrial disorders and other neurogenerative conditions is reviewed, with specific emphasis on the prospects for neuroprotection. Drug Dev. Res. 46:57–66, 1998. © 1998 Wiley-Liss, Inc.
https://doi.org/10.1002/(sici)1098-2299(199901)46:1<57::aid-ddr9>3.0.co;2-rDisease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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