bims-curels Biomed News
on Leigh syndrome
Issue of 2026–02–01
seven papers selected by
Cure Mito Foundation



  1. Endocr Metab Immune Disord Drug Targets. 2026 Jan 15.
       INTRODUCTION: Mitochondrial diseases refer to a group of hereditary disorders involving damage to high-energy-consuming tissues, such as muscles, nerves, and the heart. Mitochondrial DNA (mtDNA) mutations account for most cases, but the timely identification and treatment of these conditions remain challenging.
    CASE PRESENTATION: This report describes a case of a 36-year-old male patient who was diagnosed with diabetes in 2017 and subsequently experienced recurrent diabetic ketoacidosis and seizures. On May 20, 2022, he presented with cognitive impairment, unsteady gait, and an elevated blood lactate level. Brain MRI and mitochondrial gene sequencing on peripheral blood cells revealed destructive neuronal lesions and a mutation of m.3243A>G in the MT-TL1 gene with a ratio of 6.04%, which supported the diagnosis of mitochondrial encephalomyopathy associated with lactic acidosis and stroke-like episodes (MELAS) and mitochondrial diabetes mellitus (MDM). Treatment with insulin, fluid replacement, ketoacidosis correction, diazepam, and phenobarbital relieved most symptoms. However, his blood glucose was poorly controlled. Four months after discharge, the patient suffered a relapse. Although therapies to combat infection, reduce blood glucose, and correct ketoacidosis improved his condition, the patient died in 2023 due to cerebral infarction.
    CONCLUSION: This case embodies the typical manifestations of mitochondrial diseases, emphasizing the urgency of prompt diagnosis and symptom management, which largely depends on effective genetic screening.
    Keywords:  Mitochondrial diabetes; mitochondrial DNA.; mitochondrial encephalomyopathy associated with lactic acidosis and stroke-like episodes (MELAS)
    DOI:  https://doi.org/10.2174/0118715303419754251125093050
  2. Mitochondrion. 2026 Jan 23. pii: S1567-7249(26)00002-4. [Epub ahead of print]87 102112
      Primary mitochondrial diseases (PMDs) are directly linked to oxidative phosphorylation (OXPHOS) dysfunction. Here, we investigated the selective sensitivity of PMD patient fibroblasts compared to healthy control primary human skin fibroblasts (PHSF) to ferroptosis, and the role of iron in this cell death mechanism. To address this, we investigated sensitivity to ferroptosis inducers, the effects of iron supplementation, and intracellular iron pools. The selectivity of PMD fibroblasts ferroptotic cell death was found to be more pronounced with class 1 ferroptosis inducers (FINs) that deplete GSH than upon direct GPX4 inhibitors. Notably, exogenous iron discriminatory triggered ferroptosis in patient fibroblasts and enhanced BSO-induced cell death in both patient and control cells. Further study revealed elevated basal levels of labile iron in patient fibroblasts, but mRNA analysis of iron-regulating genes did not reveal major expression differences. These findings suggest that increased labile iron predisposes PMD fibroblasts to ferroptosis. Complementation of defective OXPHOS restored ferroptosis sensitivity and LIP levels in a cell line with an NDUFS7 mutation, indicating a functional relationship caused by OXPHOS deficiency. Further understanding this interplay may provide insights into therapeutic strategies targeting iron homeostasis to mitigate ferroptotic cell death in PMDs.
    Keywords:  Ferroptosis; Labile iron pool; Primary mitochondrial disease
    DOI:  https://doi.org/10.1016/j.mito.2026.102112
  3. Ann Fam Med. 2026 Jan 26. 24(1): 75-76
      When my patient accidentally told me he loved as I was leaving his hospital room, it made me think about how we end encounters and how we could do better. Physicians leave patient encounters multiple times a day, yet we receive no teaching or guidance on how to end an encounter. If we hurry away after a challenging encounter, what does that convey to the patient about the impact they have or don't have on us? Since that afternoon with my patient, I've made a habit of pausing outside of rooms before moving on, especially after deeply difficult or uncomfortable conversations. It feels like one small thing I can do to demonstrate that, no matter the awkwardness or challenge, I will not abandon them.
    Keywords:  communication; non-abandonment; physician-patient relationship
    DOI:  https://doi.org/10.1370/afm.250275
  4. Pharmaceut Med. 2026 Jan 28.
      The increasing complexity of healthcare decision making and the demand for real-world evidence call for a transformation in how Medical Affairs departments generate and communicate evidence. In response, AstraZeneca Spain implemented a structured stakeholder-driven framework aligned with the Clinical Evidence 2030 and Medical Affairs 2030 visions, aiming to deliver high-impact, timely, and tailored insights across each therapeutic area. An ambitious evidence generation vision was developed around two core components: (1) enhanced therapeutic area knowledge leading to improvements in guideline-directed medical therapy for patients and (2) strategic use of evidence for the company, leading to improved efficiency in delivering healthcare innovation for patients. The first component encompasses a broad spectrum of study modalities, such as the generation of real-world data on the use of medicines, health economics and outcomes research, predictive analytics, clinical management, and patient experience studies using diverse data sources, including real-world databases, registries, and electronic health records. Studies address different research questions and data gaps, including disease burden, treatment patterns, economic modeling, patient experience through ethnographic research, and knowledge derived from artificial intelligence-driven analytics. The second component seeks to ensure that the evidence generated is used strategically. First, it should be the basis for the development of a powerful Value Story that conveys the clinical, economic, and humanistic value of a pharmaceutical product and creates confidence in regulators, payers, and prescribers, thereby strengthening its therapeutic positioning. Second, the evidence generated needs to be presented to stakeholders in a dynamic manner, enhancing decision-making processes and fostering real-time engagement with healthcare providers and payers. Here, we present a data visualization tool that was developed to this end, termed ATLAS. Third, results from real-world evidence studies can be used to inform outcome-based agreements with payers. This type of innovative value strategy that goes beyond traditional financial agreements represents a method to ensure that the clinical and economic value delivered by a product is reflected in healthcare pricing and reimbursement models, facilitating broader access and timely patient care. AstraZeneca Spain's evidence generation approach represents a significant contribution to the evolution of Medical Affairs into a strategic driver of healthcare innovation and, ultimately, patient benefit. It implies an effort in the consolidation of unique features such as the increase in robust methodological capabilities and versatility in the design of studies, the leverage of predictive analytics, the development of advanced data visualization tools, the emphasis on patient-centered research, and the collaboration with partners expert in emerging technologies. The ultimate goals of an ambitious evidence generation vision like this are to provide the data needed for decision making at all levels, to identify opportunities to enhance diagnosis, to accelerate access to innovative therapies, and to ensure more patients receive optimal care.
    DOI:  https://doi.org/10.1007/s40290-025-00599-2
  5. BMC Neurol. 2026 Jan 27.
      
    Keywords:  Alzheimer disease; Dementia; Erythropoietin; Neurodegenerative diseases; Neuroprotection; Parkinson disease
    DOI:  https://doi.org/10.1186/s12883-026-04627-9
  6. Int J Dev Neurosci. 2026 Feb;86(1): e70100
       BACKGROUND: Autism spectrum disorder (ASD) has a strong genetic basis, yet specific etiological factors remain unidentified in the majority of cases. Mitochondrial DNA (mtDNA) variations have been hypothesized as potential contributors to ASD development. However, the precise role of mtDNA remains unclear due to inconsistent findings across studies, which often suffer from methodological limitations.
    AIMS: This study aimed to comprehensively investigate the association between mtDNA variants, gene-level variant burden and haplogroup distributions in a Turkish paediatric ASD cohort.
    STUDY DESIGN: Case control study.
    METHODS: Whole mtDNA analysis of peripheral blood samples from 95 children with ASD and 95 healthy controls was performed using next-generation sequencing. Identified variations were evaluated for pathogenicity via genomic databases and in silico analyses. Potentially pathogenic variations underwent segregation analysis. Additionally, mtDNA haplogroup distributions were compared between the groups.
    RESULTS: The overall frequency of mtDNA variants was significantly higher in the ASD group than in the control group (p = 0.033). The ASD cohort harboured 23 distinct variants (initially classified as three pathogenic/likely pathogenic (P/LP) and 20 variants of uncertain significance [VUS]); while the control group had 13 VUS and no P/LP variants. Gene-based burden analysis identified a significantly higher variant load in the MT-CYB gene within the ASD cohort (FDR = 0.048). However, segregation analysis of the P/LP variants (including m.827A > C, m.9804G > A and a novel MT-CYB variant) revealed maternal inheritance from asymptomatic mothers. Consequently, all P/LP variants were reclassified as VUS. No significant difference was found in mtDNA haplogroup distribution between groups.
    CONCLUSION: Through comprehensive mtDNA scanning and rigorous pathogenicity assessment, our findings suggest that mtDNA variations are not implicated in the pathogenesis of ASD. However, given the complex nature of ASD, future research is needed with larger sample sizes, standardized pathogenicity assessment criteria and detailed phenotypic analyses to further elucidate the relationship between mtDNA variants and ASD.
    Keywords:  autism spectrum disorder; genetic variation; haplotypes; high‐throughput nucleotide sequencing; mitochondrial DNA; segregation analysis
    DOI:  https://doi.org/10.1002/jdn.70100
  7. Annu Rev Med. 2026 Jan;77(1): 381-398
      With the pharmacokinetics, dosing, safety, and manufacturing of approved or investigational drugs already well-characterized, drug repurposing and repositioning offer emerging strategies to rapidly develop effective treatments for various challenging diseases. However, the growing mass of genetic and multiomics data has not been effectively explored by the drug repurposing community due to a lack of accurate approaches. This review aims to be an authoritative, critical, and accessible review and discussion of general interest to the drug repurposing community concerning the use of artificial intelligence (AI) and machine learning (ML) tools. Emerging questions include what is achievable with AI in this domain and what its impact will be, what AI and ML embrace, and how we, as geneticists, pharmacologists, and computational scientists, can contribute to the discovery of new, inexpensive, and affordable repurposable medicines. The fast growth of genetics and multiomics data (genomics, transcriptomics, proteomics, metabolomics, and radiomics) and electronic health records in diverse populations contributes to answering questions, including how to rapidly identify effective repurposable medicines, what a clinically meaningful effect size in trials is, and what the potential implications for precision medicine are. This review discusses AI and ML for drug repurposing in the context of genetics, multiomics, real-world data collection, and crowdsourcing of knowledge. We conclude by considering questions on how AI and ML methodologies can unite the diverse aspects of translational medicine for emerging treatment development in human-challenging diseases.
    Keywords:  Alzheimer's disease; artificial intelligence; drug repurposing; electronic health records; multiomics; personalized medicine
    DOI:  https://doi.org/10.1146/annurev-med-050224-122802