bims-curels Biomed News
on Leigh syndrome
Issue of 2025–12–07
thirteen papers selected by
Cure Mito Foundation



  1. J Clin Invest. 2025 Dec 01. pii: e187571. [Epub ahead of print]135(23):
      Deficits in the mitochondrial energy-generating machinery cause mitochondrial disease, a group of untreatable and usually fatal disorders. Refractory epileptic events are a common neurological presentation of mitochondrial disease, including Leigh syndrome, a severe form of mitochondrial disease associated with epilepsy. However, the neuronal substrates and circuits for mitochondrial disease-induced epilepsy remain unclear. Here, using mouse models of Leigh syndrome that lack mitochondrial complex I subunit NDUFS4 in a constitutive or conditional manner, we demonstrated that mitochondrial dysfunction leads to a reduction of GABAergic neurons in the rostral external globus pallidus (GPe) and identified a specific affectation of pallidal Lhx6-expressing inhibitory neurons contributing to altered GPe excitability. Our findings revealed that viral vector-mediated Ndufs4 reexpression in the GPe effectively prevented seizures and improved survival in the models. Additionally, we highlight the subthalamic nucleus (STN) as a critical structure in the neural circuit involved in mitochondrial epilepsy, as its inhibition effectively reduces epileptic events. Thus, we have identified a role for pallido-subthalamic projections in epilepsy development in the context of mitochondrial dysfunction. Our results suggest STN inhibition as a potential therapeutic intervention for refractory epilepsy in patients with mitochondrial disease, providing promising leads in the quest to identify effective treatments.
    Keywords:  Epilepsy; Inflammation; Mitochondria; Mouse models; Neuroscience
    DOI:  https://doi.org/10.1172/JCI187571
  2. Health Expect. 2025 Dec;28(6): e70524
    Widening Engagement Patient Advisory Group
       BACKGROUND: Drug development practices for rare diseases promote a promissory notion that the drug pipeline will succeed (with the next new drug/drug trial) and an imaginary of widening patient engagement (often desired but yet to be enacted). Contemporary industry practices of patient engagement are shaped by this promissory, and engagement often includes limited patient perspectives, typically relying on patients from established Patient Organisations or identified by Contract Research Organisations.
    OBJECTIVE: We sought to explore whether more deliberative methods might enable wider, more diverse patient engagement for orphan drug trials.
    DESIGN: Citizen's Jury co-designed with patient advisors.
    SETTING AND PARTICIPANTS: Results of an earlier ethnography of a biotech company's patient engagement practices, along with findings from clinical trials for patients with idiopathic pulmonary fibrosis, clinical practice and patient testimony, were presented to the Citizens' Jury made up of patients and carers.
    RESULTS: Jurors discussed and offered a 'verdict' on trial materials and processes that would optimise the engagement of more diverse patients for drug trials for rare diseases, suggesting that more could be done at an organisational level to ensure that potential trial participants were able to 'engage'. They asserted that the industry could do more to understand the unmet needs and wishes of a wider group of patients and should seek input from more diverse groups.
    DISCUSSION: The Citizens' Jury called for practices to enable wider engagement-for both drug trials and drug trial design-and more transparency about the risks associated with engagement, for individual patients and currently marginalised groups.
    CONCLUSIONS: Current drug development practices reify expert patient perspectives and often ignore the views of the wider group of patients who may participate in trials and/or use new medicines developed. More deliberative methods of engagement have the potential to democratise drug development and ensure that new medicines and trials meet the needs of a broader patient demographic.
    PATIENT OR PUBLIC CONTRIBUTION: A patient advisory group (PAG) comprising six people with IPF gave input into all aspects of the research design and conduct, including co-design of the Citizens' Jury. Two patients from international patient organisations served as a steering group (SG). Members of both groups provided their interpretations of the study findings and gave insight into their experiences in clinical design and participation.
    Keywords:  deliberative democracy; drug development; imaginaries; patient engagement; promissory, orphan drugs
    DOI:  https://doi.org/10.1111/hex.70524
  3. Res Involv Engagem. 2025 Dec 05.
       BACKGROUND: Supporting participation decisions and experiences in clinical trials is a persistent challenge that could be improved by two areas: patient engagement (PE), which involves actively collaborating with patients to enhance research relevance and value, and shared decision-making (SDM), which involves helping individuals make evidence-informed, values-based decisions about participation. The extent to which PE and SDM have informed trial recruitment interventions has not been synthesized.
    OBJECTIVES: We aimed to explore (1) how PE informed recruitment interventions, both in general and among equity-deserving populations, and whether demographic differences existed between studies using and not using PE, and (2) how SDM has informed recruitment interventions, both in general and among equity-deserving populations.
    METHODS: We identified randomized and quasi-randomized recruitment intervention studies from a prior Cochrane review and the Online Resource for Research in Clinical triAls database. We assessed recruitment interventions for reporting of PE and coded the level at which PE occurred ('substantive engagement', 'limited engagement', 'both', 'unclear', or 'no engagement') and the areas in which PE occurred (development of the research question, intervention design, selecting outcomes, dissemination/implementation, or 'other'). We coded SDM across six domains: providing information about options, probabilities, clarifying outcomes, guidance in deliberation, using evidence, and disclosure and transparency.
    RESULTS: Of the 122 recruitment intervention studies included, 37 (30.3%) reported PE, although limited engagement was most common (n = 22; 59.5%). PE was most often used in designing the recruitment intervention (n = 32; 86.5%) followed by 'other' (n = 11; 29.7%; e.g., PE supporting participant recruitment efforts), developing the research question (n = 2; 5.4%), selecting outcomes (n = 3; 8.1%), and dissemination/implementation (n = 3; 8.1%). SDM was occasionally reported (n = 25; 20.5%), most commonly as 'providing information about options' (n = 11; 9.0%). Equity-deserving populations were the focus of 24 studies (19.7%); 11 of these also used PE (9.0%).
    CONCLUSIONS: Efforts to improve trial participation have not been informed by literature around patient lived experiences. Recruitment interventions infrequently reported any PE and occasionally mentioned SDM. When PE was mentioned, it was usually limited. These results hold among studies involving equity-deserving populations. Greater consideration of PE and SDM could enhance trial recruitment, research impact, trial participation experiences, and equity in trial recruitment.
    Keywords:  Clinical trial; Equity-deserving; Methodology review; Patient and public involvement; Patient engagement; Patient partner; Recruitment interventions; Shared decision making; Systematic review; Trial participation
    DOI:  https://doi.org/10.1186/s40900-025-00806-z
  4. Jugan Geongang Gwa Jilbyeong. 2024 Feb 29. 17(8): 345-350
      Rare diseases require long-term treatment and management because disease-related information is limited. Furthermore, their causes and symptoms are very complex, which make full recovery and cure very challenging. Accordingly, annual celebrations are held to strengthen patients' and families' will to overcome and improve awareness of rare diseases among the public and policymakers. In 2008, the European Organization for Rare Diseases established the last day of February as "World Rare Disease Day" and has been conducting an annual campaign. The Republic of Korea also changed the Rare Disease Day to the same day as World Rare Disease Day through a law amendment in 2023. The year 2024 is significant. It will be the first time we celebrate the "Rare Disease Day" anniversary on the last day of February. A commemorative event and symposium will be held on this day to reflect its meaning.
    Keywords:  Awareness; Rare disease day; World rare disease day
    DOI:  https://doi.org/10.56786/PHWR.2024.17.8.4
  5. Med Teach. 2025 Dec 03. 1-9
       INTRODUCTION: Medical students are exposed to sensitive topics throughout their university education. Topics can be sensitive based on an individual's life experience, and common examples include domestic violence and mental health. Teaching sensitive topics risks re-traumatisation, and educators typically receive little training in balancing harm minimisation and maximising preparedness to handle distressing patient encounters. A trauma-informed medical education (TIME) approach has been proposed, aiming to optimise the learning environment, improve resilience and prepare students for practice. However, perceptions of TIME and which approaches students find effective remain incompletely understood.
    METHODS: We conducted a descriptive, qualitative study design using semi-structured interviews with sixteen medical students from Monash University, Australia. We recruited students in their final years who had completed their general practice rotation, and interviews were recorded and transcribed verbatim. We undertook reflexive thematic analysis of transcripts using NVivo software.
    RESULTS: The overarching theme was the generation of a 'Safe Space' to learn sensitive topics. Contributing elements included sub-themes of (1) Preparedness for Teaching, (2) Teaching Techniques, and (3) Debriefing.
    DISCUSSION: Students reported that many TIME strategies were already in place in their teaching. The findings highlighted that trauma-informed teaching strategies were effective in promoting medical student psychological safety and well-being.
    Keywords:  Trauma-informed medical education; medical education; psychological safety; sensitive topics
    DOI:  https://doi.org/10.1080/0142159X.2025.2593499
  6. Hum Gene Ther. 2025 Dec 01.
      Cell and gene therapies present unique challenges for long-term follow-up as they may lead to adverse events that could emerge years after treatment. Long-term follow-up helps identify potential delayed adverse events, such as oncogenesis or immunogenicity, which might not manifest immediately after treatment. Current regulatory guidelines emphasize a risk-based approach, recommending follow-up durations based on the therapy's mechanism of action between 5 and 15 years. To facilitate long-term monitoring, regulatory authorities recommend the establishment of long-term follow-up protocols, often involving patient registries and supported by real-world data sources to systematically capture and track data from treated patients. These long-term follow-ups are instrumental in both post-approval safety studies and reimbursement decisions, where payers may link payments to treatment outcomes. As the field of cell and gene therapy evolves, regulatory frameworks continue to adapt, balancing the need for comprehensive long-term follow-up with the feasibility of implementation to ensure that therapies are adequately monitored, ensuring patient safety and therapeutic effectiveness over time. However, maintaining patient engagement over extended periods, ensuring high-quality data collection, and addressing privacy concerns present significant challenges. Innovative solutions such as decentralized data collection, digital health technologies, and data linkage with electronic health records aim to alleviate patient burden and improve data reliability.
    Keywords:  cell and gene therapy; clinical registries; efficacy; long-term follow-up; regulations; safety
    DOI:  https://doi.org/10.1177/10430342251403439
  7. Jugan Geongang Gwa Jilbyeong. 2024 Mar 07. 17(9): 351-366
      There are difficulties in diagnosis and counseling after genetic testing, due to the increase in the rate of diagnostic results arising from the development of genetic testing techniques and the discovery of mutations with unclear pathogenicity derived from next-generation sequencing. By presenting examples of additional support provided for the interpretation of results after genetic testing and subsequent genetic counseling support, we attempted to present a system that seeks to resolve difficulties that may generally be experienced in the post-genetic testing process. Fifteen cases of interpretation support were provided through the post-genetic-testing result-interpretation support project under the support of the Korea Disease Control and Prevention Agency, and effective genetic counseling support was provided accordingly. Diagnostic support through the interpretation of results after genetic testing was aimed at resolving the diagnostic odyssey of rare genetic diseases. Moreover, support for appropriate diagnoses can reduce the social and economic burdens. We propose a national-level management system for medical genetics team services covering treatment, testing, and counseling.
    Keywords:  Genetic counseling; Genetic testing; Rare diseases
    DOI:  https://doi.org/10.56786/PHWR.2024.17.9.1
  8. Aust Health Rev. 2025 Aug 07. pii: AH25051. [Epub ahead of print]49(4):
      There is increasing recognition of the benefits of robust data infrastructures, capacity building for a data informed society, and strategic policy and financial support to enable data integration (also known as data linkage). However, despite widespread availability of data, and recognition of the value of data linkage and investment in this area, data linkage continues to be complex, timely, and costly, and these elements are often underestimated by researchers. In this article, we introduce data linkage basics for Australian researchers and discuss important considerations for those embarking on healthcare research that utilises data linkage.
    Keywords:  administrative health data; data integration; data linkage; health outcomes; research
    DOI:  https://doi.org/10.1071/AH25051
  9. J Pediatr Gastroenterol Nutr. 2025 Nov 29.
       OBJECTIVES: Chronic intestinal failure (CIF) is a rare and complex disease, requiring home parenteral nutrition (HPN) to sustain growth and development. The impact on parents taking care for children with HPN remains underexplored. This qualitative study aimed to elucidate the experiences and challenges faced by parents in caring for HPN-dependent children.
    METHODS: Parents of children aged 0-18 years, diagnosed with CIF receiving HPN in the Emma Children's Hospital-Amsterdam UMC, were eligible. One-to-one semistructured interviews were conducted with parents at their home with open-ended questions regarding experiences around diagnosis, experiences with healthcare (both home care and at the hospital), mental health, holidays, social functioning and leisure time, work, relationship with the partner and family, fear for the future, and overall impact.
    RESULTS: Parents of 24 children were invited. Thirteen parents (four fathers and nine mothers) of 10 children (four females, median age 9 years) with HPN agreed to participate and were interviewed. Most important recurring themes among all parents, emerging from open-ended questions, were as follows: control in caregiving and reluctance to trust others to provide care over their child, social isolation due to limited time and flexibility, and importance of maintaining their own identity by self-fulfillment activities such as work, and physical or social activities.
    CONCLUSIONS: This qualitative study underlines the profound impact of managing a child with HPN on daily life, relationships and well-being. There is need for tailored support and interventions to help families face the burden of having a child with HPN.
    Keywords:  interviews; intestinal failure; parents; pediatrics; quality of life
    DOI:  https://doi.org/10.1002/jpn3.70286
  10. Front Digit Health. 2025 ;7 1664110
      Smartphone-based health applications offer promising opportunities for personalized and continuous monitoring in healthcare. However, many apps remain confined to research settings and are never implemented in clinical practice. Moreover, the development and implementation of apps for rare diseases is significantly lagging behind. This perspective outlines six key themes critical to the successful development and implementation of health apps, drawing on insights from Dutch stakeholders. These include: stakeholder collaboration, development, ownership, financing, integration into hospital-based care, and patient use. Our perspective additionally discusses specific barriers, including regulatory constraints, funding challenges, and usability limitations, alongside facilitators such as co-creation with end users, early stakeholder involvement, implementation planning, and leveraging existing care networks. Specific challenges for rare diseases, such as limited patient populations, funding constraints, and difficulties in clinical validation and regulatory compliance, are also addressed, with potential solutions proposed. This perspective offers concrete recommendations to support the transition of health apps from research to clinical practice. Sustainable implementation requires early and ongoing stakeholder engagement, flexible strategies adapted to small-scale contexts, a strong focus on end users' needs, and an impact-driven implementation plan already established at the start of development.
    Keywords:  digital health; implementation; rare diseases; smartphone application; stakeholder management
    DOI:  https://doi.org/10.3389/fdgth.2025.1664110
  11. Eur J Hum Genet. 2025 Dec 01.
      As early rapid genomic sequencing (rGS) is adopted in paediatric medicine, there is an urgency to understand and address family support needs. This mixed methods study (Peregrin*) examined the experiences of 96 parents, 1-5 years after receiving trio rGS results for their child with a severe early-onset condition. Quantitative outcome measures assessed parental well-being, life satisfaction, and family impact, comparing results to non-clinical population data, between mothers and fathers, and according to child's diagnostic outcome. Qualitative semi-structured interviews explored parents' satisfaction with support, engagement with support networks, and unmet needs. Quantitatively, mothers exhibited elevated anxiety and depression relative to population norms, and there was a lack of strong correlation in well-being metrics within couples. Parents of children with a genomic diagnosis reported poorer well-being, explained by greater medical complexity. Qualitatively, insufficient support was more frequently reported by those whose child had received a genomic diagnosis (36%) compared to those without (6%). Families drew on a range of formal and informal support sources, including condition-specific groups, though these were accessed by a minority of fathers. These findings highlight persistent and evolving support needs in families affected by complex childhood health conditions, which persist after rGS. Parents' support needs are highly individual, vary over time and across children's illness trajectory. There remain important gaps between parental needs and support, impacting on family well-being.
    DOI:  https://doi.org/10.1038/s41431-025-01987-7
  12. BMC Health Serv Res. 2025 Dec 01.
      
    Keywords:  Health communication; Medical records; Patient centered care; Patient discharge summaries; Patient empowerment; Patient engagement
    DOI:  https://doi.org/10.1186/s12913-025-13774-7
  13. J Bioeth Inq. 2025 Dec 01.
      The partnership approach is part of a broader shift in healthcare that seeks to empower patients in their own care. Accompanying patients (APs) extend the concept of peer support. They are experienced patients who engage directly and individually with new patients, enhancing the partnership model. However, the ethical foundations of this role and the ethical tensions arising from its integration are underexplored. To identify the key skills and values required by APs and the ethical tensions they experience, we conducted a qualitative study based on in-depth interviews with nineteen APs between January and May 2021 in Québec, Canada. Interviews explored motivations, skills, values, and experiences in healthcare institutions. Thematic analysis was complemented by Tannahill's public health ethics framework to interpret the ethical tensions identified. The core values identified for this role were empathy, respect, and altruism. All participants agreed that experiential knowledge was paramount. APs identified independence from healthcare institutions as the key to connecting and developing a trusting relationship with patients. However, they also expressed a need to be part of the healthcare system to ensure the sustainability of their role. Our results show an ethical tension between the philosophical core of APs and their needs to pursue their functions. We conclude that independence and authenticity as an AP is not necessarily incompatible with institutionalization, professionalization, and remuneration. These can be achieved if AP programmes are aligned with the philosophy of patient partnership, structured with flexible criteria, and remain self-regulated.
    Keywords:  Accompanying patient; Ethical foundations; Ethics; Patient advisor; Patient expert; Patient navigator; Patient partner; Patient partnership; Public health; Public health ethics
    DOI:  https://doi.org/10.1007/s11673-025-10482-z