bims-curels 2026-08-30 papers

Issue of 2026–08–30
five papers selected by
Cure Mito Foundation

Genes (Basel). 2026 Jul 23. pii: 850. [Epub ahead of print]17(8):

Advances in Primary Mitochondrial Diseases: Diagnosis, Natural History Studies and Clinical Trials.

Albert Z Lim, Aye-Myat Moe, Renae J Stefanetti, Yi Shiau Ng.

Primary mitochondrial diseases (PMDs) are one of the most common genetic disorders with an estimated prevalence of 1 in 4300. This review article summarises the latest updates in the field of mitochondrial medicine over the last decade. The availability of exome and genome sequencing in clinical practice has empowered clinicians to unravel the phenotypic heterogeneity of PMD and to end the diagnostic odyssey experienced by many patients and families. In unresolved cases, the detection of variant(s) of unknown significance by next-generation sequencing creates diagnostic and clinical uncertainties, and integrating a multi-omics approach can improve diagnostic yield. Alongside breakthroughs in genomic technologies, there is growing interest in using fluid biomarkers to guide diagnosis, monitor disease progression, and potentially serve as clinical trial endpoints. However, the clinical application of these fluid biomarkers in unselected patient cohorts with different disease onset and phenotypes would require more robust evidence. Natural history studies derived from national and international collaborations have provided insights into genotype-phenotype relationships and prognostic factors across several genotypes, including m.3243A>G, MT-ATP6, POLG, and TK2. Advances in therapeutic discoveries and clinical trials are challenging the obsolete dogma that PMDs are untreatable and bringing hope to patients; four compounds have been licensed, and many trials are in progress. Many barriers and challenges to translating laboratory discoveries into clinical therapy in PMD remain, including preclinical models for efficacy and safety testing, sample size, trial design, and the selection of outcome measures and trial endpoints.

Keywords: fluid biomarkers; outcome measures; phenotypes; trial endpoints; whole-genome sequencing

DOI: https://doi.org/10.3390/genes17080850

Res Involv Engagem. 2026 Aug 25. pii: 133. [Epub ahead of print]12(1):

Compensating patient partners on health research teams: a qualitative descriptive study of barriers, facilitators, and implications for equity, diversity, and inclusion in Canadian patient-oriented research.

Mwalu Peeters, Kimberly Strain, Shelley Doucet, Adrienne Gulliver, Anna Samson, Sarah Bridges, Amy Ma, Samantha Fowler, Dawn P Richards, Ravneet Somal, Madeline Levesque, Kathryn Asher, Alison Luke.

BACKGROUND: Research teams increasingly rely on patient engagement-where patients are engaged as partners in knowledge production-to improve the quality and relevance of health research. An ongoing challenge is how best to compensate patient partners for their time and expertise, given diverse personal, financial, and institutional contexts. This study identifies common barriers and facilitators to patient partner compensation; examines how compensation practices actively shape who can participate in patient-oriented research, enabling or constraining equity, diversity, and inclusion within health research teams; and explores strategies to mitigate barriers to equitable compensation and boost diverse and inclusive patient engagement in health research.
METHODS: Using a qualitative descriptive design, and with active involvement from patient partners on our research team, we recruited geographically and socially diverse participants from across the spectrum of patient-oriented research in Canada, including patient partners, research staff, administrative and finance employees, and funding organization staff. Semi-structured interviews (n = 25) and focus groups (10 in number, n = 24), conducted between 2023 and 2025, elicited respondents' impressions of the interactions between patient partnership, compensation practices, and equity, diversity, and inclusion. We applied inductive thematic analysis to identify shared values and common experiences, and explore solutions to compensation practices that challenge equitable patient engagement.
RESULTS: Thematic analysis of interviews and focus groups generated seven themes: Clear expectations and processes, Bureaucratic inertia, Reproduction of privilege, Institutional mistrust, Tax and benefit implications, Funding cycles, and Relational dynamics.
CONCLUSION: Compensation is an integral component of effective patient-oriented research and has significant implications for research engagement among structurally marginalized communities. We propose recommendations for advancing equitable and inclusive compensation practices within Canadian patient-oriented research.

Keywords: Compensation; Equity, diversity, and inclusion; Honoraria; Patient and public involvement; Patient-oriented research; Payment; Power dynamics; Relationality; Relationship building; Research engagement

DOI: https://doi.org/10.1186/s40900-026-00961-x

Curr Opin Pharmacol. 2026 Aug 27. pii: S1471-4892(26)00058-5. [Epub ahead of print]90 102662

Mitochondria as a therapeutic platform in inflammatory and degenerative disorders: mechanisms, biomarkers, and translational challenges.

Lamiaa M ElAbbasy.

Mitochondrial dysfunction has emerged as a convergent pathogenic mechanism across inflammatory and degenerative disorders, functioning not as a passive consequence but as an active amplifier of tissue injury, immune dysregulation, and impaired repair. Consistently observed mitochondrial abnormalities include excessive reactive oxygen species production, impaired oxidative phosphorylation, defective mitophagy, altered fission-fusion dynamics, and release of mitochondrial danger-associated molecular patterns, particularly cell-free mitochondrial DNA (cf-mtDNA), which serves both as a proinflammatory mediator and a potential circulating biomarker of disease activity. These alterations create self-reinforcing networks in which mitochondrial stress promotes innate immune activation, sustains inflammatory signaling, and accelerates structural or functional decline in vulnerable tissues. Mitochondria-targeted pharmacology has expanded rapidly, encompassing organelle-directed antioxidants, modulators of mitochondrial quality control, biogenesis or metabolic enhancers, nano-enabled delivery platforms, and emerging mitochondrial replacement strategies. Despite strong mechanistic appeal and encouraging preclinical data, clinical translation remains limited by the absence of validated pharmacodynamic biomarkers, an incomplete understanding of disease endotypes, inconsistent tissue target engagement, delivery barriers to mitochondria-rich compartments, and poor predictive value of animal models for human disease biology. The cf-mtDNA and related mitochondrial signatures are increasingly attracting attention for patient stratification, phenotyping, and therapeutic monitoring, although assay standardization remains unresolved. This review focuses on the core mechanisms that link mitochondrial dysfunction to disease progression. It also examines biomarker development and the major barriers to translation. Emerging approaches such as nanotechnology and mitochondrial replacement are discussed as supplementary strategies, not as the main focus of the review.

DOI: https://doi.org/10.1016/j.coph.2026.102662

Health Expect. 2026 Aug;29(4): e70832

Trust As the Foundation for Informed Decision-Making in Prenatal Genetic Screening and Diagnostic Testing: A Qualitative Study.

Miller Finkelstein, Christina Collart, Lenicia Jenkins, Richard Frankel, Norah Crossnohare, John Bridges, Monique Katsuki, Susannah Rose, Marsha Michie, Megan Allyse, Michael Rothberg, Marissa Coleridge, Brownsyne Tucker-Edmonds, Ruth M Farrell.

BACKGROUND: Prenatal genetic screening and diagnostic testing (PS&D) requires pregnant patients to make time-sensitive, high-stakes decisions that often involve multifaceted risk assessments and deeply personal values. These decisions are becoming increasingly complex as the clinical integration of new genomic science and technologies advances alongside parallel changes in maternal-foetal medicine, neonatology, and reproductive health services. Despite these changes, there is limited guidance on how best to prepare patients to formulate PS&D decisions with significant implications for obstetric outcomes. The goal of this study was to characterise pregnant patients' perceptions of the decision-making process and identify facilitators and barriers for them to make informed decisions about their PS&D options.
METHODS: We conducted a qualitative study of pregnant and postpartum individuals receiving obstetric care within a large healthcare system. Participants, enroled across early pregnancy, late pregnancy, and postpartum periods, completed in-depth semi-structured interviews exploring their experiences, preferences, and needs related to PS&D decision-making. Interviews were recorded, transcribed verbatim, and analysed by a multidisciplinary team using inductive thematic analysis, supported by iterative coding, memoing, and theme identification.
RESULTS: Most participants were < 35 years of age (48 of 61) and had a prior pregnancy (42 of 61). Four major subthemes emerged around a central concept of trust affecting medical decision-making: (1) Trust as a means of navigating the complexity of PS&D: Patients relied heavily on their obstetric (OB) providers to interpret complex information and guide decisions, particularly as testing decisions became more consequential and time sensitive. (2) Trust as a prerequisite for informed decision-making: Patients emphasised that psychological safety and relational continuity were necessary before they could ask questions, disclose concerns, or integrate medical information with personal values. (3) Erosion of trust due to perceived bias, judgement, or assumptions: Provider bias, whether expressed through communication style, assumptions about patient preferences, or perceived judgement, undermined trust and impeded informed, values-aligned decisions. (4) Structural barriers in prenatal care models: Limited continuity, time constraints, and triaged group-based care created obstacles to building trust and compounded difficulties in discussing sensitive topics across multiple providers.
CONCLUSIONS: Our findings suggest that trust is a core component of informed PGT decision-making and central to supporting patient-centred communication amid uncertainty, cascading decisions, and evolving genomic technologies. Strategies to build and maintain trust, particularly within multi-provider prenatal care models, are essential to enabling informed, values-concordant prenatal decision-making. System-level interventions that promote continuity, unbiased communication, and structured agenda-setting help strengthen prenatal care delivery and improve patient experience and outcomes.
PATIENT OR PUBLIC CONTRIBUTION: Patients were involved in three main aspects of the study: (1) identifying the need for research that supports PS&D decision-making through our prior work with patients as part study participation in focus groups, interviews, and survey studies, (2) contributing to the development of the interview guide through direct feedback to the instrument's questions and methods of data collection, and (3) participating in the study interview and providing their perspectives on how to support them and other pregnant patients as they face a myriad of pre and posttest decisions.

DOI: https://doi.org/10.1111/hex.70832