bims-curels Biomed News
on Leigh syndrome
Issue of 2026–07–19
thirteen papers selected by
Cure Mito Foundation
  1. Karnofsky performance scale and modified Rankin scale as indicators of functional capacity in patients with mitochondrial disease.
  2. Headache in mitochondrial diseases: From migraine to stroke-like episodes.
  3. Navigating the Mitochondrial Maze: A Case Report of Emergent Cesarean Delivery After Labor Induction in a Patient With Leigh Syndrome.
  4. A phase III double-blind, placebo-controlled, randomized withdrawal trial of 5‑aminolevulinic acid hydrochloride with sodium ferrous citrate for efficacy and safety in patients diagnosed as Leigh syndrome.
  5. Beyond innovation: why rare disease gene therapy needs a reset.
  6. "It didn't feel like anything unusual because we had already been through so much": Disability-Related Research Experiences of Families with Children Enrolled in the Undiagnosed Diseases Network.
  7. Nanoengineering Systems for Gene Therapy: Mechanisms, Modalities, and Future Directions.
  8. The Value of a Medical Home for Children with Medical Complexity from the Perspective of Their Families.
  9. Improving international medical students' communication skills in psychosomatic care through a communication training seminar: a natural language processing-based analysis.
  10. The Recommendation Paradox: Perspectives on Genetic Testing in Huntington's Disease Families.
  11. A systematic scoping review on quality criteria for clinical practice guidelines for rare diseases.
  12. The Role of Social Value in Data-Intensive Health Research.
  13. "What is data?" Learnings from paediatric patient and sibling involvement in co-producing a research communication tool for children and young people.
  1. Neurol Sci. 2026 Jul 15. pii: 629. [Epub ahead of print]47(8):
    Karnofsky performance scale and modified Rankin scale as indicators of functional capacity in patients with mitochondrial disease.
    Jasmin A Koskiniatis, Mika H Martikainen.
       BACKGROUND: Mitochondrial diseases are genetic multisystem disorders. Only symptomatic treatment is available, and clinical progression is common. We investigated whether two commonly used quantitative measures of functional capacity, modified Rankin scale (mRS) and Karnofsky Performance scale (KPS) scores, could be determined retrospectively based on electronic patient records (EPRs) and whether they provided insights into disability and disease progression.
    METHODS: Previously identified 52 patients (28 women) with clinically and genetically confirmed mitochondrial disease at Turku University Hospital (TUH, Turku, Finland) were investigated. Genetic diagnoses were the m.3243 A > G mitochondrial DNA (mtDNA) variant (N = 21), other pathogenic mtDNA variants (N = 22), and nuclear gene variants causing mitochondrial disease (N = 9). Mean age was 50 years (range 10-85 years); average follow-up was nine years. Available neurology and emergency medicine EPRs were reviewed, and mRS and KPS scores determined.
    RESULTS: Patients harbouring the m.3243 A > G, other mtDNA variants, or nuclear gene variants were compared. In all groups, functional capacity declined over time. Those with m.3243 A > G had lower first and latest KPS and mRS values than those with nuclear gene variants (p < 0.004 for all). Differences between the m.3243 A > G and other pathogenic mtDNA variants were not significant.
    CONCLUSION: Functional decline seems a common feature in mitochondrial disease. The KPS and mRS scales may offer a simple tool for long-term evaluation of the functional capacity of patients with mitochondrial disease, especially in non-specialist and primary healthcare. Further studies are needed to confirm whether patients with nuclear gene defects are at particular risk of progression.
    Keywords:  Functional capacity; Genetics; Mitochondrial disease; Performance scales
    DOI:  https://doi.org/10.1007/s10072-026-09212-z
  2. Headache. 2026 Jul 14.
    Headache in mitochondrial diseases: From migraine to stroke-like episodes.
    Matteo Azzimonti, Samuel Padelli, Dario Ronchi, Simona Sacco, Giacomo Pietro Comi, Stefania Corti.
       OBJECTIVE: Headaches in primary mitochondrial diseases (PMDs) present distinctive features that warrant differentiation from primary headache disorders. Current knowledge on clinical manifestations, pathophysiology, diagnosis, and treatment is here reviewed.
    BACKGROUND: Among the most frequent and disabling symptoms affecting patients with PMDs, headache occurs in approximately 55-71% of individuals. Those with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and related phenotypes are particularly affected. Compared to the general population, migraine prevalence in patients with PMD is up to three- to four-fold higher.
    METHODS: To examine headache across the full spectrum of PMDs, a narrative literature review was conducted. PubMed, Scopus, and Web of Science databases were searched using the terms "mitochondrial disease," "migraine," "headache," "MELAS," and "stroke-like episodes," with no date restrictions. Relevant references from identified articles were also reviewed.
    RESULTS: In PMDs, migraine with or without aura is the most common type of headache disorder, especially among carriers of the m.3243A>G mutation, the most prevalent pathogenic variant found in MELAS syndrome. Recent data from Mendelian randomization studies have suggested a potential causal link between low mitochondrial DNA copy number and migraine without aura. The clinical characteristics that help differentiate headache in PMDs include protracted or atypical aura, co-occurring neurological and systemic manifestations, temporal relationship with stroke-like episodes, and variable response to conventional therapy. The use of mitochondrial cofactors such as riboflavin, coenzyme Q10, and L-arginine as adjuncts to standard preventive strategies has been supported by only limited evidence.
    CONCLUSIONS: Specialized diagnostic and therapeutic approaches are required for headache management in PMDs, combining mitochondrial-targeted interventions with evidence-based headache treatments. When atypical migraine features are present, particularly prolonged aura or aura occurring with epileptic seizures or encephalopathy, evaluation for underlying mitochondrial disease should be considered.
    Keywords:  MELAS; headache; migraine; primary mitochondrial disorder; stroke‐like episodes
    DOI:  https://doi.org/10.1111/head.70180
  3. A A Pract. 2026 Jul 01. 20(7): e02247
    Navigating the Mitochondrial Maze: A Case Report of Emergent Cesarean Delivery After Labor Induction in a Patient With Leigh Syndrome.
    Nancy H Greenspon, Nicole Higgins, Jacob M Nieb.
      Leigh syndrome is a rare mitochondrial disorder characterized by progressive psychomotor regression. Due to high childhood mortality and rare adult-onset cases, there are no guidelines for the obstetric management of this population. In these patients, physiological stress from labor may precipitate acute decompensation, manifesting with metabolic acidosis and multiorgan failure. We report the obstetric anesthetic management of a patient with adult-onset Leigh syndrome who required an emergent intrapartum cesarean delivery after labor induction. This case highlights the necessity of tailored anesthetic strategies to mitigate mitochondrial dysfunction and supports the potential safety of essential peripartum medications previously undocumented in this population.
    DOI:  https://doi.org/10.1213/XAA.0000000000002247
  4. PLoS One. 2026 ;21(7): e0332283
    A phase III double-blind, placebo-controlled, randomized withdrawal trial of 5‑aminolevulinic acid hydrochloride with sodium ferrous citrate for efficacy and safety in patients diagnosed as Leigh syndrome.
    Akira Ohtake, Yuichi Abe, Kei Murayama, Hideaki Shiraishi, Hitoshi Osaka, Satoko Kumada, Tetsuya Ito, Hidehito Kondo, Yusuke Hamada, Sayaka Suzuki-Ajihara, Masato Arao, Yuki Ueda, Kohei Nagai, Keiko Ichimoto, Ayako Matsunaga, Hirofumi Kashii, Yoko Nakajima, Hitoshi Nakagawa, Shunichi Kurose, Kaori Fukuda, Kiwamu Takahashi, Mitsugu Yamauchi, Motowo Nakajima.
       OBJECTIVE: A phase III, double-blind, placebo-controlled, randomized withdrawal trial of SPP‑004 (5‑aminolevulinic acid hydrochloride and sodium ferrous citrate) was conducted to confirm the efficacy and safety of SPP-004 for maintenance of clinical response in patients diagnosed with Leigh syndrome (LS) showing central nervous system disorders.
    METHODS: Fifty-four patients entered a 24-week open-label period of SPP-004 administration. Among them, 28 patients who showed improvement on the Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) for cranial nervous symptoms and myopathy symptoms proceeded to a 48-week double-blind (DB) period, where they were randomized (1:1) to receive SPP‑004 or placebo (n = 14 each). Efficacy was evaluated using NPMDS for the full analysis set (FAS) during the DB‑period (SPP-004 n = 13, Placebo n = 14) and the entire study period (n = 54). Safety evaluation focused on adverse events (AEs) in all 54 patients administered SPP-004.
    RESULTS: The primary endpoint, the proportion of patients who discontinued due to inadequate efficacy at 48 weeks, was lower in the SPP-004 group (15.4% [95% CI: 1.9-45.4%]) compared to the placebo group (50.0% [23.0-77.0%]). Over 80% of the SPP-004 group showed maintained efficacy (p = 0.0486). All adverse drug reactions were mild, with no notable differences in AEs between groups.
    CONCLUSION: These findings suggest that SPP-004 is safe and may provide therapeutic effect for LS patients who achieved an initial clinical response.
    DOI:  https://doi.org/10.1371/journal.pone.0332283
  5. Expert Opin Biol Ther. 2026 Jul 16.
    Beyond innovation: why rare disease gene therapy needs a reset.
    Maram E Abdalla Elsayed, Robert E MacLaren.
      
    Keywords:  Adeno-associated virus; European Medicines Agency; Food and Drug Administration; cell therapy; clinical trials; gene therapy; natural history; rare disease; translation; translational development
    DOI:  https://doi.org/10.1080/14712598.2026.2706035
  6. Genet Med. 2026 Jul 13. pii: S1098-3600(26)00981-0. [Epub ahead of print] 102663
    "It didn't feel like anything unusual because we had already been through so much": Disability-Related Research Experiences of Families with Children Enrolled in the Undiagnosed Diseases Network.
    Undiagnosed Diseases Network
       PURPOSE: In recent years, researchers have brought attention to the underrepresentation of people with disabilities in biomedical research, including genomics research. However, little is known about how disability-related experiences influence participation in rare disease research. This omission is striking, because rare diseases are associated with disabling phenotypes that affect multiple body systems. As part of a study interrogating the relationship between rare disease status and disability identity, we conducted mixed-methods research to address this knowledge gap.
    METHODS: Parents of children enrolled in the UDN (n=25) completed semi-structured interviews to assess disability-related experiences in research participation. Directed content analysis was used to identify common themes.
    RESULTS: Participants' disability-related research experiences were characterized by: 1) disability-related facilitators to research participation, including benefits of research participation and disability-conscious approaches; 2) disability-related logistical barriers to research participation; and 3) research procedures, and the perception of research as minimally burdensome relative to clinical encounters.
    CONCLUSION: Parents of children in the UDN make considerable investments of time and resources to accommodate their children's disabilities to facilitate their participation. Future research should explore these issues in other genomic research studies and practical approaches to mitigating barriers and employing facilitators to disability-related research participation.
    Keywords:  List of Keywords: disability inclusion in genomics research; UDN; and social implications of genetics and genomics; ethical; legal; qualitative research; rare/undiagnosed diseases
    DOI:  https://doi.org/10.1016/j.gim.2026.102663
  7. Int J Mol Sci. 2026 Jul 03. pii: 5988. [Epub ahead of print]27(13):
    Nanoengineering Systems for Gene Therapy: Mechanisms, Modalities, and Future Directions.
    Raheem Mais, Ayush Kumar, Armand Ahmetaj, Gaby Burgos-Crespo, Mary Margarette Sanchez, Dianne Claire Roxas, Christopher Dcosta, Azhar Ilyas, Michael Hadjiargyrou, Steven Zanganeh.
      Nanotechnology has become an important platform in the fields of gene therapy and genome editing, providing delivery strategies that address persistent therapeutic challenges by improving the precision, efficiency, and safety of genetic modifications. This review highlights the central role of nanomaterials in overcoming persistent barriers to genetic interventions, including inefficient delivery, instability of genetic cargo, and off-target effects. Specifically, we emphasize the combined use of nanomaterials with clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) systems, which can improve editing specificity and therapeutic efficacy. Beyond the classical CRISPR/Cas9 platform, this review also discusses next-generation modalities such as base editors, Cas13, prime editing, and the recently described Tandem Interspaced Guide RNA and TIGR-associated protein (TIGR-Tas) system, while considering their therapeutic potential and distinct delivery challenges. By using nanomaterials, the stability and intracellular delivery of genome-editing systems are improved, enabling more effective treatments for genetic disorders and acquired diseases such as cancer and infectious diseases. In addition, nanocarriers provide controlled release, protection from degradation, and better biocompatibility, thereby improving the safety and reliability of gene-editing therapies. Despite these advances, important translational challenges remain, including immunotoxicity, large-scale manufacturing, and regulatory integration. Overall, the continued convergence of nanotechnology and genome engineering may support the development of personalized medicine strategies that adapt genetic engineering tools for patient-specific applications.
    Keywords:  CRISPR-Cas systems; gene therapy; genetic disorders; genome engineering; nanomaterials; nanotechnology; targeted delivery
    DOI:  https://doi.org/10.3390/ijms27135988
  8. Acad Pediatr. 2026 Jul 14. pii: S1876-2859(26)00186-5. [Epub ahead of print] 103404
    The Value of a Medical Home for Children with Medical Complexity from the Perspective of Their Families.
    Kristina E Malik, Ashley Dafoe, Kate Holler, Brooke Dorsey, Christopher J Stille.
       OBJECTIVE: To identify what families value in a medical home for children with medical complexity (CMC).
    METHODS: This was a qualitative study using semi-structured interviews with caregivers of CMC recruited from a single complex care program. Participants identified their child's medical home during the interview and described experiences which made it a medical home. Transcripts were coded and themes were developed through iterative team discussions using thematic analysis; a parent partner was on the team from grant development through publication.
    RESULTS: During semi-structured interviews with 17 caregivers of CMC, 94% identified a medical home. Caregivers identified it was valuable for a medical home to provide comprehensive whole child care through curiosity to learn, a willingness to problem solve, and bi-directional trusting relationships that reduced the mental load on families. Caregivers gave specific examples where the synergy of these components improved CMC and family outcomes.
    CONCLUSION: These results support the current definition of a pediatric medical home for CMC and also introduce the novel idea that having a medical home has a positive outcome of reducing the mental load on families. This study suggests ensuring delivery of care concordant with the medical home principles can support the needs of CMC.
    Keywords:  CMC; CYSHCN; children and youth with special health care needs; children with medical complexity; medical home; pediatrics; primary care
    DOI:  https://doi.org/10.1016/j.acap.2026.103404
  9. BMC Med Educ. 2026 Jul 11. pii: 1155. [Epub ahead of print]26(1):
    Improving international medical students' communication skills in psychosomatic care through a communication training seminar: a natural language processing-based analysis.
    Julia Sgrott, Christoph Nikendei, Ede Nagy, Aleksei Smirnov, Josefina Arias Alvarado, Hans-Christoph Friederich, Ivo Dönnhoff.
       BACKGROUND: International students face numerous challenges in both their academic and social lives when relocating to a new country for their university studies. The foreign language can have an impact on international medical students' performance in patient encounters. Particularly in the context of psychosocial medicine, a deficiency in communication skills can negatively impact the doctor-patient-relationship. This is the first study that uses natural language processing (NLP) as well as traditional rating scales to assess the improvement of international students' communication skills after attending a communication training seminar.
    METHODS: N = forty-two international students participated in the study, which followed a pre-post-design. Diagnostic interviews with standardized patients (SP) were videotaped before and after the three-day training seminar, which was comprised of short lectures and communication trainings with SPs regarding the topic of psychosomatic medicine. Transcripts of diagnostic interviews were analyzed with NLP. Videotaped clinical encounters were assessed by three raters with binary and global rating instruments. For the comparison between pre- and post-assessment of all NLP communication parameters and rating results, two-way ANOVAs and Wilcoxon tests were calculated, respectively.
    RESULTS: NLP communication parameter results showed a decrease in talk-turns, interruptions, number of questions and talking over, and an increase in talk-turn-length in post-assessment compared to pre-assessment. There were no significant pre-post changes observed in binary checklist results. Significant pre-post changes were observed in global rating score and ratings from global rating domains 'interview structure' and 'verbal expression'.
    CONCLUSION: International students significantly improved their communication style in psychosomatic medicine towards a more patient-centered approach. Changes in NLP communication parameters and improved interview style and verbal expression suggest that international students may have listened to patients more carefully. Furthermore, NLP has shown to be a viable tool to evaluate communication parameters in a doctor-patient-relationship and assess the effectiveness of communication training for international students.
    Keywords:  Communication training; International students; Natural language processing; Patient-centered communication
    DOI:  https://doi.org/10.1186/s12909-026-09890-5
  10. J Genet Couns. 2026 Aug;35(4): e70265
    The Recommendation Paradox: Perspectives on Genetic Testing in Huntington's Disease Families.
    Noit Inbar, Achinoam Socher, Aya Bar David, Penina Ponger, Nurit Omer, Adi Reches, Yael Manor, Tanya Gurevich.
      Huntington's disease (HD) families face complex decisions about predictive genetic testing and reproductive options, including preimplantation genetic testing (PGT), and particularly PGT for Monogenic Disorders (PGT-M). We examined attitudes toward genetic testing and reproductive options across affected groups within HD families (e.g., people with HD, spouse/caregivers, and at-risk family members), in a healthcare system with full funding for genetic services. We conducted semi-structured interviews with 51 participants (17 people with HD, 20 at-risk relatives, 14 spouses/partners), recruited from the National HD Clinic in Tel Aviv, Israel. Framework Analysis was employed to enable systematic comparison across groups. Three themes emerged from the analysis: "Surprised by HD" revealed that family members were often unaware of genetic risk despite predictable inheritance, reflecting patterns of nondisclosure and misdiagnosis; "Truth or luck" captured divergent attitudes toward predictive testing, with some participants advocating for early knowledge while others emphasized the psychological burden of knowing in the absence of a cure. Together, these themes formed the context for a central finding: "The recommendation paradox", a striking pattern where individuals who avoided or regretted personal predictive testing nonetheless strongly endorsed reproductive options for offspring, a tension that manifested differently across groups depending on their relationship to HD. The recommendation paradox reveals ethical tensions between reproductive autonomy and emerging expectations of genetic responsibility. This pattern persists even when economic barriers are removed, demonstrating that psychological factors remain primary determinants of testing uptake. Genetic counseling should explicitly address divergent attitudes toward personal versus offspring testing, recognizing that support for prevention does not necessarily indicate readiness for personal testing.
    Keywords:  Huntingtons disease; genetic counseling; preimplantation genetic testing; qualitative research; reproductive decision‐making
    DOI:  https://doi.org/10.1002/jgc4.70265
  11. Syst Rev. 2026 Jul 16.
    A systematic scoping review on quality criteria for clinical practice guidelines for rare diseases.
    Iméze J Hieltjes, Mirthe J Klein Haneveld, Ingeborg Van Dusseldorp, Charlotte M W Gaasterland, Johanna H van der Lee.
       BACKGROUND: Rare diseases impose substantial challenges on affected individuals and healthcare systems. While clinical practice guidelines (CPGs) are crucial for standardizing care, tools to assess their trustworthiness are limited, particularly for rare diseases. There is a need for minimum quality criteria to ensure CPG reliability and utility.
    OBJECTIVE: This systematic scoping review aims to identify a set of criteria that can be used for evaluating and endorsing CPGs for rare diseases.
    METHODS: A systematic scoping review was conducted using four databases (Ovid/Medline, Embase.com, Scopus, and Google Scholar) from inception to April 9, 2024. The search was developed by a medical information specialist. Titles and abstracts were independently screened by two reviewers, with disagreements resolved through discussion or a third reviewer. Articles were included if they addressed quality criteria for guidelines on rare diseases in general, excluding disease-specific guidelines.
    RESULTS: From 9587 unique titles, only one study met the inclusion criteria. The included study, published by Hilton-Boon et al. (2015), summarized an international workshop on the applicability of AGREE II criteria for rare disease guidelines.
    CONCLUSION: Our systematic review identified a single report detailing an international workshop that evaluated the utility of the AGREE II instrument for assessing two guidelines focused on rare diseases. This limited finding highlights a significant gap in methodologies tailored to the specific complexities of rare disease guidelines. The findings underscore the need for a tailored, streamlined set of criteria to address the unique challenges of rare disease guidelines, supporting their development, evaluation, and endorsement in clinical practice.
    DOI:  https://doi.org/10.1186/s13643-026-03247-1
  12. Bioethics. 2026 Jul 16.
    The Role of Social Value in Data-Intensive Health Research.
    Tessa I van Rijssel, Sam H A Muller, Marianne Boenink, Johannes J M van Delden.
      Data-intensive health research complicates traditional requirements for informed consent, due to the amount of data contributors and data points, the open-ended nature of research questions, and repeated or secondary data use. To still enable data-intensive health research, there is a move towards other-generally lower-standards for consent such as opt-out systems, in current developments such as the European Health Data Space (EHDS). This is premised on the social value that data-intensive health research is assumed to provide through advancing research and innovation. Traditionally, social value functions both as a fundamental requirement for research, as well as a ground to justify individual risk in research ethics. However, ongoing debates surrounding data-intensive health research suggest that social value can also be used to justify lower standards of consent. Here, social value seems to obtain an additional and distinct function. This raises questions on the role of social value in research ethics and evaluations of the acceptability of research. In this paper, we examine three possible roles of social value: (i) to prevent research waste and set research priorities; (ii) to justify exposing research participants to risk; and (iii) to lower standards for consent. We discuss the presuppositions underlying these various roles. When social value is invoked to justify lower consent standards, this specifically impacts data contributors' ability to have control over when and how their data are used. Therefore, we propose that this use of social value requires arranging alternative forms of meaningful involvement and control for data contributors.
    Keywords:  broad consent; data‐intensive health research; informed consent; public interest; research ethics; social value
    DOI:  https://doi.org/10.1111/bioe.70159
  13. Res Involv Engagem. 2026 Jul 17. pii: 115. [Epub ahead of print]12(1):
    "What is data?" Learnings from paediatric patient and sibling involvement in co-producing a research communication tool for children and young people.
    Intensive-Share Group
      Empowering children and young people (CYP) to actively participate in research development is essential to ensure impactful outcomes. Meaningful involvement helps researchers to pose relevant questions, design acceptable methodologies, and disseminate findings effectively. However, the inclusion of CYP in research, particularly in paediatric intensive care (PIC), is rarely reported. This is partly due to the challenging PIC environment, and most patient and public involvement and engagement activities (PPIE) focus only on the parents' experience and perspective. The Intensive-Share group was established in Scotland in 2022 to facilitate PPIE activity in PIC research. The group includes family members with a range of lived experiences with the youngest member aged 7 years. They meet regularly to contribute to various aspects of research including research design, study materials and procedures, and public engagement. This article describes the co-production approach adopted in the 'What is data?' Project, which was co-created with researchers based on an idea from the Intensive-Share group. The project aimed to co-develop a short-animated video to explain healthcare data research to CYP in an engaging and accessible format. CYP meaningfully participated in all stages of the project and were integral to its success. Initial evaluations indicated the animation was well-received by families and they self-reported improved understanding of and willingness to participate in research. Co-production with CYP can be resource-intensive and challenging, but this project demonstrated it was feasible and incredibly valuable. Meaningful and authentic involvement challenged the research teams assumptions on inclusive language and the nature and level of involvement CYP preferred. Adopting a broader approach to PPIE in PIC research to include paediatric patients and siblings, perhaps on a national level, could facilitate similar initiatives in research communication and co-production. The open-source animated video is available as a resource to the wider research community to aid communication about paediatric healthcare data research.
    Keywords:  Children and young people; Co-production; Communication; Healthcare data; Paediatric research.; Patient involvement; Siblings
    DOI:  https://doi.org/10.1186/s40900-026-00924-2
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