bims-curels Biomed News
on Leigh syndrome
Issue of 2025–09–14
twelve papers selected by
Cure Mito Foundation
  1. Structural insights into DdCBE in action enable high-precision mitochondrial DNA editing.
  2. Mending a mother's mitochondrial DNA.
  3. Assessing a Mitochondrial Disease Treatment via a Novel Statistical Technique for Accelerometer Data.
  4. A Doctor Who Never Forgets What It's Like to Be a Patient.
  5. Patients as partners in medical publications: the ISMPP journey of engagement.
  6. Mitochondrial Transplantation Therapy: A Novel Approach in the Era of Organelle-Centered Regenerative Medicine.
  7. HTA Evidence in Rare Diseases: Just Rare or Also Special?
  8. A Review of the Importance and Relevance of Real-World Data and Real-World Evidence.
  9. The Experiences of Patients With Rare Diseases in Pennsylvania: A Community-Based Study.
  10. Human brain organoids: an innovative model for neurological disorder research and therapy.
  11. When physicians become patients: A podcast series for learning from patient experiences.
  12. Improving Patient Engagement in Phase 2 Clinical Trials With a Trial-Specific Patient Decision Aid: Development and Usability Study.
  1. Mol Cell. 2025 Sep 03. pii: S1097-2765(25)00701-4. [Epub ahead of print]
    Structural insights into DdCBE in action enable high-precision mitochondrial DNA editing.
    Jiangchao Xiang, Wenchao Xu, Jing Wu, Yaxin Luo, Chengyu Liu, Yaofeng Hou, Jia Chen, Bei Yang.
      DddA-derived cytosine base editor (DdCBE) couples transcription activator-like effector (TALE) arrays and the double-stranded DNA (dsDNA)-specific cytidine deaminase DddA to target mitochondrial DNA (mtDNA) for editing. However, structures of DdCBE in action are unavailable, impeding its mechanistic-based optimization for high-precision-demanding therapeutic applications. Here, we determined the cryo-electron microscopy (cryo-EM) structures of DdCBE targeting two native mitochondrial gene loci and combined editing data from systematically designed spacers to develop WinPred, a model that can predict DdCBE's editing outcome and guide its design to achieve high-precision editing. Furthermore, structure-guided engineering of DddA narrowed the editing window of DdCBE to 2-3 nt while minimizing its off-target (OT) editing to near-background levels, thereby generating accurate DdCBE (aDdCBE). Using aDdCBE, we precisely introduced a Leber hereditary optic neuropathy (LHON)-disease-related mutation into mtDNA and faithfully recapitulated the pathogenic conditions without interference from unintended bystander or OT mutations. Our work provides a mechanistic understanding of DdCBE and establishes WinPred and aDdCBE as useful tools for faithfully modeling or correcting disease-related mtDNA mutations.
    Keywords:  DdCBE; DddA engineering; cryo-EM structure; editing precision; editing window; mitochondrial DNA; mitochondrial disease modeling
    DOI:  https://doi.org/10.1016/j.molcel.2025.08.016
  2. Nat Med. 2025 Sep 12.
    Mending a mother's mitochondrial DNA.
    Mike May.
      
    DOI:  https://doi.org/10.1038/d41591-025-00056-2
  3. Ann Clin Transl Neurol. 2025 Sep 12.
    Assessing a Mitochondrial Disease Treatment via a Novel Statistical Technique for Accelerometer Data.
    Ian W McKeague, Kristin Engelstad, Yue Ge, Amber Tucker, Shufang Li, Jasim Uddin, Ziwei Zhao, John L P Thompson, Michio Hirano.
       OBJECTIVE: Therapeutic development for mitochondrial diseases, rare genetic disorders with pathogenic defects of oxidative phosphorylation, is hindered by unsatisfactory outcome measures. To address this problem, we provide the first clinical application of a novel, bias-adjusted outcome measure of acceleration across a range of subjects' activities to assess nucleoside therapy for thymidine kinase 2 deficiency, an ultra-rare autosomal recessive mitochondrial disease.
    METHODS: Data were collected from treated patients in an ongoing phase 2 clinical trial who served as their own controls. If there is a treatment effect, time-in-activity curves for these patients will increase over successive clinic visits. We used a combination of functional data analysis and longitudinal mixed-effects linear regression, adjusted for age and gender, to test for the effect of treatment length on time-in-activity.
    RESULTS: For 14 patients with at least two assessments 6 months apart, we found a significant overall improvement of time-in-activity due to treatment. Improvement was especially significant at two individual activity levels within the range (0.14 and 2 g). In longitudinal analyses, using data on time-in-activity at these two levels for all clinic visits of 19 subjects, the effect of treatment length on time-in-activity was highly significant at both 0.14 g (0.04, CI 0.01-0.08, p = 0.023) and 2 g (0.01, 0.00-0.02, p = 0.013).
    INTERPRETATION: This small-N exploratory analysis using a new accelerometer-based activity measure featuring powerful data reduction and adjustment for circadian rhythms and other biases finds that nucleoside therapy may increase activity levels in thymidine kinase 2 deficiency patients.
    Keywords:  accelerometer; mitochondrial disease; outcome measure; thymidine kinase 2 deficiency
    DOI:  https://doi.org/10.1002/acn3.70180
  4. Acad Med. 2025 Sep 08.
    A Doctor Who Never Forgets What It's Like to Be a Patient.
    Rebecca E Kaiser.
      
    DOI:  https://doi.org/10.1097/ACM.0000000000006265
  5. Curr Med Res Opin. 2025 Sep 09. 1-8
    Patients as partners in medical publications: the ISMPP journey of engagement.
    Simon R Stones, Dawn Lobban, Catherine Skobe, Nichola Gokool, Trishna Bharadia, Anna Geraci, Robert J Matheis.
      Patient engagement (PE) has evolved from an emerging concept to a fundamental ethos underpinning healthcare research and communication. In this commentary, we explore the historical evolution in medical research from patients being participants in clinical trials to becoming integral partners in communicating medical research findings. The progression from "why" to "how" PE should occur represents a fundamental shift in the medical publication landscape. We also highlight the International Society for Medical Publication Professionals' (ISMPP) journey in embracing and advancing PE within medical publications through ISMPP's initiatives and activities, including the establishment of its PE Task Force, patient membership, and support programs, while examining the cultural transformations occurring within the profession. Looking ahead, we discuss opportunities for expanding patient roles, improving accessibility to tools and frameworks, and integrating patient perspectives into leadership positions. This commentary serves as both a reflective narrative and a call to action for medical publication professionals to champion authentic and meaningful PE, ensuring publications truly engage and serve the patients at the heart of the research they describe, as exemplified by ISMPP.
    Keywords:  ISMPP; Patient engagement; medical publications; patient authorship; patient involvement; patient partnership
    DOI:  https://doi.org/10.1080/03007995.2025.2556317
  6. Front Biosci (Landmark Ed). 2025 Aug 18. 30(8): 37006
    Mitochondrial Transplantation Therapy: A Novel Approach in the Era of Organelle-Centered Regenerative Medicine.
    Ha Rim Shin, Gaheon Lee, Kyung Hwa Kim.
      Mitochondria play crucial roles in maintaining health and influencing disease progression by acting as central regulators of cellular homeostasis and energy production. Dysfunctions in mitochondrial activity are increasingly recognized as key contributors to various pathologies, ultimately impacting healthspan and disease outcomes. However, traditional treatments often do not restore damaged mitochondria to a healthy state. Mitochondrial transplantation, a cellular organelle-based therapy in which mitochondria are introduced into a recipient, has emerged as a novel concept in next-generation therapeutics that overcomes the limitations of current cell-based treatments. This review highlights the unique properties of mitochondria as therapeutic agents, including their ability to restore cellular functions and treat a wide range of diseases. In this review, we focus on the unique role of mitochondria in the regulation of stem cell functions, including stem cell fate, self-renewal, and differentiation. Various perspectives have been explored to better understand mitochondrial transplantation therapy, which harnesses the capacity of mitochondria as living drugs in regenerative medicine, as an innovative strategy to bridge the gap between cell therapy and organelle-based treatments and overcome current clinical barriers.
    Keywords:  mesenchymal stem cell; mitochondrial dysfunction; mitochondrial transplantation; organelle transplantation; regenerative medicine
    DOI:  https://doi.org/10.31083/FBL37006
  7. Pharmacoeconomics. 2025 Sep 09.
    HTA Evidence in Rare Diseases: Just Rare or Also Special?
    Anirban Basu, Simu K Thomas, Richard H Chapman, Jason Spangler.
      Manufacturers of orphan drugs face several obstacles in meeting health technology assessment requirements because of poor availability of natural history data, small sample sizes, single-arm trials, and a paucity of established disease-specific endpoints. There is a need for specific considerations and modified approaches in health technology assessments that would account for the challenges in orphan drug development. Multistakeholder collaborations can benefit patients, their families, and the broader society and reduce the inequity faced by patients with rare diseases.
    DOI:  https://doi.org/10.1007/s40273-025-01538-4
  8. Med Sci Monit. 2025 Aug 27. 31 e951118
    A Review of the Importance and Relevance of Real-World Data and Real-World Evidence.
    Dinah V Parums.
      Real-world data are routinely collected data associated with patient health status or delivery of health care from sources including patient registries, electronic health records (EHRs), medical claims data, or digital health technologies. Real-world evidence is generated from specified clinical real-world data and includes evidence of the use, benefits, and risks of a medical product. Analysis of real-world data is the basis of real-world evidence to support the use and potential benefits or risks of a medical product. Also, real-world insights are generated when real-world evidence is interpreted or applied by different stakeholders in the healthcare industry to inform the planning of clinical research studies, identifying research questions, relevant patient or disease groups, disease trends over time, and evaluating the commercial viability of a study, which can improve healthcare planning and implementation. The importance of standardizing and regulating the conduct and reporting of real-world studies is highlighted by the increasing number of registered studies. This article aims to review the continued importance and relevance of real-world evidence from real-world studies and data to support and refine interpretations from controlled clinical trials.
    DOI:  https://doi.org/10.12659/MSM.951118
  9. Public Health Rep. 2025 Sep 07. 333549251362711
    The Experiences of Patients With Rare Diseases in Pennsylvania: A Community-Based Study.
    Jonathan H Sussman, Mert Marcel Dagli, Shira L Wald, Saad S Akhtar, Keanu Natan, Jessica A Xu, Alexander Li, Brian Dawson, William C Welch.
       OBJECTIVE: Rare diseases collectively affect approximately 30 million people in the United States. Despite advances in genomic medicine, early diagnosis is challenging because of limited awareness of, accessibility to, and disparities in health care resources. We assessed the real-world experiences of patients with rare diseases in Pennsylvania and evaluated the effect of delayed diagnosis on psychosocial and financial burdens.
    METHODS: The Pennsylvania Rare Disease Advisory Council conducted a Rare Disease Needs Assessment Survey from September 2020 through January 2023. The survey, distributed through multiple channels, collected responses from patients, caregivers, and rare disease advocates in Pennsylvania. We analyzed quantitative and qualitative data on diagnosis, health care access, financial burden, and psychosocial support.
    RESULTS: A total of 1214 respondents participated, representing a diverse spectrum of rare diseases and demographic groups. More than half (57.8%) of respondents indicated diagnostic delays of ≥1 year, which were associated with additional misdiagnoses, increased annual spending, out-of-state travel, and reduced work and school hours; however, diagnostic delays were not associated with disease category. Many respondents (48.5%) reported >$5000 in annual spending related to care for their rare disease, and 24.9% were unable to access medications because of financial reasons. Diagnostic delays were associated with worse perspectives on the efficacy of care across multiple domains even after a correct diagnosis was achieved. Patients aged 0 to 20 years had a faster time to diagnosis than patients aged >20 years did.
    CONCLUSION: Patients with rare diseases in Pennsylvania face substantial barriers to diagnosis, specialized care, and financial support. Despite policy initiatives, gaps remain in genetic testing access, specialist availability, and psychosocial resources. Addressing these issues through improved diagnostics, expanded access to care, and targeted policy changes is essential to enhancing patient outcomes and quality of life.
    Keywords:  crowdsourcing; health disparities; patient advocacy; public health; rare diseases
    DOI:  https://doi.org/10.1177/00333549251362711
  10. Front Cell Neurosci. 2025 ;19 1658074
    Human brain organoids: an innovative model for neurological disorder research and therapy.
    Hancheng Li, Junxiao Zhu, Jieyu Li, Yangkai Wu, Chaohua Luo, Yuting Huang, Jieru Wu, Wenhua Liu, Hongwu Wang, Zhixian Mo.
      The emergence of human brain organoids (hBOs) has transformed how we study brain development, disease mechanisms, and therapy discovery. These 3D in vitro neural models closely mimic the cellular diversity, spatial structure, and functional connectivity of the human brain, providing a groundbreaking platform that outperforms traditional 2D cultures and animal models in studying neurodevelopment and neurological disorders. To further explore the potential of hBOs technology, we review current literature focusing particularly on its applications for diagnosing and treating major neurological diseases such as Alzheimer's disease, Parkinson's disease, and other related neurological disorders. Using patient-derived induced pluripotent stem cells combined with cutting-edge gene-editing technologies, hBOs enable highly precise mechanistic studies and scalable drug screening. Moreover, we further discuss the advantages and current limitations of hBOs. Despite these challenges, hBOs remain a transformative platform for the development of targeted neurotherapeutics. Collectively, this review offers a solid foundation for advancing neuroscience research and fostering innovative treatment strategies for neurological disorders.
    Keywords:  disease modeling; human brain organoids; induced pluripotent stem cells; neurological disorders; therapeutic innovation
    DOI:  https://doi.org/10.3389/fncel.2025.1658074
  11. PEC Innov. 2025 Dec;7 100423
    When physicians become patients: A podcast series for learning from patient experiences.
    M A van Helvoort, K J A van Dijsseldonk, B Post.
      
    Keywords:  Communication; Education; Healthcare professionals; Medical; Patients; Podcast
    DOI:  https://doi.org/10.1016/j.pecinn.2025.100423
  12. J Med Internet Res. 2025 Sep 10. 27 e71817
    Improving Patient Engagement in Phase 2 Clinical Trials With a Trial-Specific Patient Decision Aid: Development and Usability Study.
    Iva Halilaj, Relinde Lieverse, Cary Oberije, Lizza Hendriks, Charlotte Billiet, Ines Joye, Brice Van Eeckhout, Anke Wind, Anshu Ankolekar, Philippe Lambin.
       Background: Making informed decisions about clinical trial participation can be overwhelming for patients due to the complexity of trial information, potential risks and benefits, and the emotional burden of a recent diagnosis. Patient decision aids (PDAs) simplify this process by providing clear information on treatment options, empowering patients to actively participate in shared decision-making with their doctors. While PDAs have shown promise in various health care contexts, their use in clinical trials, particularly in the form of trial-specific patient decision aids (tPDAs), remains underused.
    Objective: This study aims to address the challenge of patient comprehension of traditional clinical trial materials. We developed a freely accessible, user-friendly tPDA within the context of the ImmunoSABR phase 2 trial. The tPDA aimed to enhance informed decision-making regarding trial participation. The primary endpoint was usability, quantitatively measured by the System Usability Scale (SUS). Secondary endpoints included time spent on the tPDA, patient satisfaction ratings, and participants' self-reported level of understanding of the trial.
    Methods: We developed the tPDA following the International Patient Decision Aid Standards and validated it through a structured, 3-phase iterative evaluation process. An initial evaluation was performed with 17 computer scientists who had expertise in biomedical applications, ensuring technical robustness. The content and usability were further refined through evaluations involving 10 clinicians and 8 medical students, focusing on clinical accuracy and user-friendliness. Finally, the tool was tested by 6 patients eligible for the ImmunoSABR trial to assess real-world applicability and patient-centered design.
    Results: Evaluations demonstrated the tPDA's effectiveness in enhancing informed decision-making, directly addressing our primary end point of usability with an overall mean SUS score of 79.4 (SD 15.9), indicative of good usability. Addressing our secondary endpoints, patients completed the tPDA efficiently, with the majority (4/6) finishing in under 30 minutes, and all but 1 within 60 minutes. Qualitative feedback highlighted significant improvements in patients' understanding of the trial details, reinforcing the tPDA's role in facilitating better patient engagement and comprehension.
    Conclusions: Our study demonstrates the feasibility and potential of tPDAs to enhance patient comprehension and engagement in clinical trials. Integrating tPDAs offers a valuable addition to traditional paper-based and verbal communication methods, promoting informed decision-making and patient-centered care.
    Keywords:  L19-IL2; clinical trials; immunotherapy; informed decision-making; participative medicine; patient decision aid; usability
    DOI:  https://doi.org/10.2196/71817
This page is being maintained by Thomas Krichel. It was last updated on 2025‒09‒14 at 2:13.