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Last update 23 Jan 2025

Multiple Mitochondrial Dysfunctions Syndrome

Last update 23 Jan 2025

Basic Info

Synonyms

MMDS - multiple mitochondrial dysfunctions syndrome, Multiple Mitochondrial Dysfunctions Syndrome, Multiple mitochondrial dysfunctions syndrome

+ [2]

Introduction

Syndrome caused by impairment of mitochondria. Whilst mitochondrial disorders may be caused by impairment of a single stage of energy production, individuals with multiple mitochondrial dysfunctions syndrome have reduced function of more than one stage. Symptoms begin in early life and affected individuals usually do not live past infancy. Symptoms include encephalopathy, hypotonia, seizures and psychomotor delay. Most affected babies have lactic acidosis that can be life threatening.

Drugs associated with Multiple Mitochondrial Dysfunctions Syndrome

MiD49

Target

DNM1L

Mechanism

DNM1L inhibitors

Active Org.

Mitobridge, Inc.

Originator Org.

Mitobridge, Inc.

Active Indication

Multiple Mitochondrial Dysfunctions Syndrome

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

KF-52

Target

PFKM

Mechanism

PFKM inhibitors

Active Org.

Kansai University

Originator Org.

Kansai University

Active Indication

Acidosis, Lactic [+1]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with Multiple Mitochondrial Dysfunctions Syndrome

NCT06080581

/ RecruitingNot ApplicableIIT

Mitochondrial Derangements Driving Muscle Insulin Resistance in Humans

The overarching aim of this observational study is to characterize muscle mitochondrial defects in individuals harboring pathogenic mitochondrial DNA (mtDNA) mutations associated with an insulin-resistant phenotype.
In a case-control design, individuals with pathogenic mtDNA mutations will be compared to controls matched for sex, age, and physical activity level. Participants will attend a screening visit and two experimental trials including:
An oral glucose tolerance test
A hyperinsulinemic-euglycemic clamp combined with measurements of femoral artery blood flow and arteriovenous difference of glucose
Muscle biopsy samples

Start Date20 Oct 2023

Sponsor / Collaborator

Rigshospitalet

[+1]

NCT01439854

/ CompletedNot ApplicableIIT

Regulation of Hepatic and Peripheral Glucose Metabolism: Protocol IVA. Effect of Plasma Glucose Reduction by Selective SLGT2 Inhibition on Mitochondrial Dysfunction and Impaired Insulin Signaling/Sensitivity in T2DM

The purpose of this study is to examine the effect of the chronic treatment of type 2 diabetes (T2DM) with dapagliflozin on: (1) mitochondrial gene function/expression and insulin signaling/action and (2) oral glucose tolerance and beta cell function. Dapagliflozin is a potent, highly specific inhibitor of renal glucose transport [SGLT2].

Start Date01 Mar 2011

Sponsor / Collaborator

University of Texas Health Science Center At San Antonio

[+1]

100 Clinical Results associated with Multiple Mitochondrial Dysfunctions Syndrome

100 Translational Medicine associated with Multiple Mitochondrial Dysfunctions Syndrome

0 Patents (Medical) associated with Multiple Mitochondrial Dysfunctions Syndrome

107

Literatures (Medical) associated with Multiple Mitochondrial Dysfunctions Syndrome

01 Jan 2025·Journal of Human Genetics

Phenotypic spectrum of iron-sulfur cluster assembly gene IBA57 mutations: c.286 T > C identified as a hotspot mutation in Chinese patients with a stable natural history

Article

Author: Tian, Xiaojuan ; Duan, Ruoyu ; Liu, Zhimei ; Fang, Fang ; Li, Jiuwei ; Jiang, Huafang ; Song, Minhan ; Li, Tongyue ; Chen, Chunhong ; Duan, Xin ; Wang, Hongmei ; Xu, Chaolong ; Han, Tongli ; Ren, Xiaotun

Mutations in IBA57 disrupt iron-sulfur clusters maturation, causing a rare mitochondrial disease. Clinical manifestations vary from neonatal lethality to childhood-onset spastic paraparesis, yet the ethnic heterogeneity and natural history remain unclear, necessitating further exploration. This study aimed to delineate the genotype-phenotype correlation of IBA57 mutations by analyzing diverse clinical presentations. We report 11 Chinese patients and include literature-reported cases, totaling 61 patients enrolled for analysis. Clinical, neuroimaging, genetic, and disease progression information were collected. Among these, 46 presented as multiple mitochondrial dysfunctions syndrome 3 (MMDS3), with 58.7% originating from Chinese population. Based on disease course, we propose three clinical subtypes: neonatal, infant and childhood subtypes. Neonatal cases universally displayed hypotonia and respiratory distress at presentation, deceased within three months. Most infancy and childhood cases exhibited developmental regression and impaired motor function. Cavitating leukoencephalopathy was a typical neuroimaging finding in MMDS3 patients. The c.286 T > C mutation was reported in 85.2% of Chinese patients. A significantly lower mortality rate was observed compared to the non-Chinese group (P = 0.002), with a survival rate exceeding 90% at 5 years, indicating a relatively stable disease progression. Fifteen cases from three families manifested the spastic paraplegia 74 phenotype, demonstrating normal development before onset, with common clinical manifestations including spastic paraplegia (14/15), visual impairment (10/13), and peripheral neuropathy (9/13). In conclusion, this study indicates a hotspot mutation in Chinese and analyses the disease progression with different clinical subtypes.

01 Sep 2024·European Journal of Pharmacology

Liraglutide alleviated alpha-pyrrolidinovalerophenone (α-PVP) induced cognitive deficits in rats by modifying brain mitochondrial impairment

Article

Author: Behmadi, Homayoon ; Ghahremani, Mohammad Hossein ; Sabzevari, Omid ; Sharifzadeh, Mohammad ; Baeeri, Maryam ; Gholami, Mahdi ; Ghahremanian, Amirhosein ; Hassani, Shokoufeh ; Foroumadi, Alireza ; Seyfi, Soheila ; Noruzi, Marzieh ; Taghizadeh, Ghorban ; Pourahmad, Jalal

The use of NPS compounds is increasing, and impairment in spatial learning and memory is a growing concern. Alpha-pyrrolidinovalerophenone (α-PVP) consumption, as a commonly used NPS, can impair spatial learning and memory via the brain mitochondrial dysfunction mechanism. Liraglutide isone of the most well-known Glucagon-Like Peptide 1 (GLP-1) agonists that is used as an anti-diabetic and anti-obesity drug. According to current research, Liraglutide likely ameliorates cognitive impairment in neurodegenerative conditions and substance use disorders. Hence, the purpose of this study is examining the effect of Liraglutide on α-PVP-induced spatial learning and memory problems due to brain mitochondrial dysfunction. Wistar rats (8 in each group) received α-PVP (20 mg/kg/d for 10 consecutive days, intraperitoneally (I.P.)). Then, Liraglutide was administered at 47 and 94 μg/kg/d, I.P., for 4 weeks following the α-PVP administration. The Morris Water Maze (MWM) task evaluated spatial learning and memory 24 h after Liraglutide treatment. Bedside, brain mitochondrial activity parameters, including reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), cytochrome c release, mitochondrial outer membrane damage and swelling, and brain ADP/ATP ratio, were studied. Our results showed that Liraglutide ameliorated α-PVP-induced spatial learning and memory impairments through alleviating brain mitochondrial dysfunction (which is indicated by increasing ROS formation, collapsed MMP, mitochondrial outer membrane damage, cytochrome c release, mitochondrial swelling, and increased brain ADP/ATP ratio). This study could be used as a starting point for future studies about the possible role of Liraglutide in ameliorating mitochondrial dysfunction leading to substance use disorder- induced cognitive impairment.

14 Aug 2024·RETINAL Cases & Brief Reports

Long Term Follow Up of a Family with A3243G Mitochondrial Syndrome

Article

Author: Feo, Alessandro ; Voichanski, Shilo ; Fossataro, Claudia ; Abraham, Néda ; Sarraf, David ; Lemon, Jack D.

Purpose:To describe the clinical and multimodal imaging (MMI) features of a family (proband, sister and mother) with A3243G mitochondrial retinopathy and long-term follow up.Methods:Medical and imaging records were retrospectively evaluated. Multimodal imaging included ultra-widefield color fundus photography, fundus autofluorescence, and spectral-domain optical coherence tomography. Long-term MMI follow up ranged from 6 to 15 years and was available for each member.Results:The proband (Case 1) exhibited rapidly progressive bilateral macular atrophy, corneal endothelial polymegathism, and an A3243G mutation in the mitochondrial DNA. The proband also endorsed a history of early-onset myocardial infarction (MI) ten years prior at the age of 42. The proband’s sister (Case 2) only exhibited unilateral focal macular atrophy but admitted to a history of severe multiorgan systemic disease, including multiple sclerosis and major depression disorder. The proband’s mother (Case 3), the only one with diabetes mellitus and hearing loss, originally presented with branch retinal vein occlusion in the right eye and pattern dystrophy in the left eye which evolved to geographic atrophy, OD > OS, 15 years later.Conclusion:A3243G mitochondrial syndrome can exhibit heterogenous ocular and systemic features, even within members of the same family. The development of the characteristic maculopathy with early-onset MI warrants genetic testing. Early cardiac and systemic screening may be recommended in individuals with characteristic retinal findings and genetic confirmation.

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