bims-curels 2025-08-31 papers

bims-curels

Biomed News

on Leigh syndrome

Issue of 2025–08–31
seven papers selected by
Cure Mito Foundation

Selective muscle MRI changes in a patient with a rare mitochondrial DNA variant causing myoclonic epilepsy with ragged red fibres.
The homoplasmic MT-TK m.8357T > C mtDNA variant as a cause of multiorgan mitochondrial disease.
Efficacy and Safety of 5-Aminolevulinic Acid Hydrochloride Combined with Sodium Ferrous Citrate in Pediatric Patients with Leigh Syndrome and Central Nervous System Disorders: An Initial Exploratory Trial with a Double-Blind Placebo-Controlled Period, Followed by an Open-Label Period and a Subsequent Long-Term Administration Study.
Clinical and Molecular Characterizations of Mitochondrial Disorders: A Tertiary-Care Center Experience.
How Do Participatory Citizenship Models Inform Co-production in Health Research? A Systematic Review.
Patient involvement in publications: qualitative mapping of the current landscape within the pharmaceutical industry.
Empowering partnership: key lessons from the co-development of patient-oriented research with parents, researchers, and healthcare professionals.

Neuromuscul Disord. 2025 Aug 13. pii: S0960-8966(25)00931-9. [Epub ahead of print]54 106204

Selective muscle MRI changes in a patient with a rare mitochondrial DNA variant causing myoclonic epilepsy with ragged red fibres.

Taylor Watson-Fargie, David G Anderson, William Stewart, Cheryl Longman, Sila Hopton, Yi Shiau Ng, Emma L Blakely, Robert W Taylor, Maria E Farrugia.

  Primary mitochondrial disease refers to a group of genetic disorders caused by pathogenic variants in either the nuclear or mitochondrial genomes, leading to an impairment of oxidative phosphorylation. We present a young female with a prominent myopathic phenotype associated with an episode of cardiac decompensation. MRI of lower limb musculature revealed a selective pattern of fatty infiltration and muscle oedema. Skeletal muscle biopsy confirmed significant evidence of mitochondrial histopathological abnormalities characterised by multiple respiratory chain deficiencies whilst complete sequencing of the entire mitochondrial genome identified a rare, likely pathogenic m.8362T>G MT-TK gene (NC_012920.1) variant at high levels of heteroplasmy, which we confirmed to be maternally-inherited.

Keywords:  MERRF; Multi-system disorder; Muscle MRI; Primary mitochondrial disorder

DOI:  https://doi.org/10.1016/j.nmd.2025.106204
Mitochondrion. 2025 Aug 18. pii: S1567-7249(25)00077-7. [Epub ahead of print]85 102080

The homoplasmic MT-TK m.8357T > C mtDNA variant as a cause of multiorgan mitochondrial disease.

Luisa Zupin, Valeria Capaci, Maria Teresa Bonati, Eleonora Lamantea, Muhammad Suleman, Andrea Marsala, Fulvio Celsi, Beatrice Spedicati, Sergio Crovella, Giulia Gortani, Giorgia Girotto, Irene Bruno, Massimo Zeviani.

  The diagnosis of disorders associated with mitochondrial DNA (mtDNA) variants presents substantial complexity due to their genetic and clinical heterogeneity, which is largely influenced by mtDNA heteroplasmy. However, the level of heteroplasmy alone is often not sufficient to predict the clinical phenotype including its severity and progression. This study concerns the characterization of the m.8357T > C variant in the MT-TK gene, encoding for mt-tRNA-Lys found in two pediatric siblings. Both had symptoms suggestive of a mitochondrial disease, including severe hearing loss, easy fatigability, decreased activity of mitochondrial complex I in muscle samples, epilepsy, metabolic acidosis with hyperkalemia, and mild kidney impairment. The m.8357T > C mtDNA variant was homoplasmic in muscle, blood, urine and fibroblasts. Immortalized fibroblasts from the patients showed reduced activity of mitochondrial complexes I, III and IV, decreased mitochondrial respiration, and abnormal depolarization of the mitochondrial membrane potential. The mt-tRNA-Lys levels were reduced as compared to the mt-tRNA-Leu (UUR) or the snRNA encoded by RNU6B nuclear gene; the level of three mitochondrial DNA encoded proteins was decreased, altogether suggesting a defective translation machinery in cells carrying the variant. Consistently, fibroblasts from the mother, who had only mild hearing loss, despite high level of heteroplasmy, showed some biochemical abnormalities, however milder than in her daughter and son. Contrariwise, their maternal aunt, who showed intellectual disability, mild hearing loss, easy fatigability and weakness was also virtually homoplasmic for the m.8357T > C in blood and urinary sediment cells. These findings suggest the pathogenicity of the m.8357T > C variant but only in condition of homoplasmy.

Keywords:  Heteroplasmy; Mitochondrial disease; mt-tRNA-Lys

DOI:  https://doi.org/10.1016/j.mito.2025.102080
Life (Basel). 2025 Jul 23. pii: 1168. [Epub ahead of print]15(8):

Efficacy and Safety of 5-Aminolevulinic Acid Hydrochloride Combined with Sodium Ferrous Citrate in Pediatric Patients with Leigh Syndrome and Central Nervous System Disorders: An Initial Exploratory Trial with a Double-Blind Placebo-Controlled Period, Followed by an Open-Label Period and a Subsequent Long-Term Administration Study.

Yuichi Abe, Toshimitsu Hamasaki, Jun Natsume, Yukiko Mogami, Kei Murayama, Hideaki Shiraishi, Yuki Abe, Satoko Kumada, Ryuta Tanaka, Kenji Ihara, Takafumi Sakakibara, Yasushi Okazaki, Hitoshi Nakagawa, Kiwamu Takahashi, Mitsugu Yamauchi, Motowo Nakajima, Akira Ohtake.

  An explorative study was conducted to evaluate the efficacy and safety of 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate (SPP-004) in 10 pediatric patients with Leigh syndrome (LS) aged 3-24 months in 10 institutions between December 2014 and July 2019. The patients were randomized and allocated to the SPP-004 or placebo group for a 12-week double-blind period, followed by a 12-week open-label period with SPP-004 and then a long-term study of up to 180 weeks. The efficacy and safety were evaluated using the Newcastle Pediatric Mitochondrial Disease Scale (NPMDS) and adverse events (AEs), respectively. No significant differences were found between groups in NPMDS scores, but prolonged SPP-004 treatment stabilized or improved scores. During the initial double-blind phase, the serum lactate levels increased in the placebo group but not in the SPP-004 group. Over the period of prolonged treatment with SPP-004, the average serum lactate level gradually decreased to a normal level. One patient died due to heart failure, presumably due to an underlying disease. Overall, 7 out of 10 patients received SPP-004 without developing severe AEs until the termination of the long-term study. Given the severe symptoms and poor prognosis of pediatric LS, NPMDS scores were indicative of stabilization in pediatric LS patients treated with SPP-004.

Keywords:  5-aminolevulinic acid; Leigh syndrome; mitochondrial disease; mitochondrial respiratory chain disorder; sodium ferrous citrate

DOI:  https://doi.org/10.3390/life15081168
Children (Basel). 2025 Aug 21. pii: 1102. [Epub ahead of print]12(8):

Clinical and Molecular Characterizations of Mitochondrial Disorders: A Tertiary-Care Center Experience.

Mohammed Almuqbil, Najla Binsabbar, Shahad Alsaif, Sulaiman Almasoud, Talah Albasry, Duaa Baarmah, Waleed Altwaijri, Ahmed Alrumayyan.

   BACKGROUND: Given the limited research on mitochondrial diseases in our area, specifically regarding their genetic variability and diverse clinical manifestations, and considering the significant number of consanguineous marriages in our region, we aimed to investigate the clinical and molecular characteristics of patients with mitochondrial disorders in Saudi Arabia.
METHODS: This retrospective cross-sectional cohort study involved a chart review of patients diagnosed with mitochondrial disorders at the Ministry of National Guard Health Affairs tertiary health care centers in Saudi Arabia between 2013 and 2022.
RESULTS: The study population comprised 116 patients with a mean age of 10 years (±7 SD). Among the study cohort, 34.5% (n = 40) had died. The primary cause of death was cardiopulmonary arrest (55.0%, n = 22). The most prevalent condition was developmental delay (67.9%). Around 56.9% were diagnosed using Whole Exome Sequencing (WES), 10.3% by Whole Genome Sequencing due to negative WES, 23.3% through a single-gene approach, 7.8% were analyzed through a mitochondrial panel, and 1.7% via a gene panel. The distributions of current age and age at diagnosis were significantly different between the nuclear and mitochondrial gene types. Notably, the diagnostic delay time (time taken from symptom onset to genetic diagnosis) averaged 1.5 years for nDNA variants compared to an average of 10 years for mDNA variants.
CONCLUSIONS: This study shows that gene type affects clinical characteristics, highlighting the importance of genetic studies in disease manifestation.

Keywords:  Saudi Arabia; disorders; genetic disorders; mitochondria; mitochondrial diseases; mitochondrial dysfunction

DOI:  https://doi.org/10.3390/children12081102
Health Expect. 2025 Aug;28(4): e70394

How Do Participatory Citizenship Models Inform Co-production in Health Research? A Systematic Review.

Catharine Rose, Lois Donnelly, Jess Howdle, Mark Lynes, Katharine Arnett, Mary Nettle, Eleanor Bradley.

   BACKGROUND: Co-production within health research has increased rapidly over the past two decades, enabling citizens to shape health policy and practice. Yet, co-production can be shallow or undemocratic, providing little opportunity for meaningful citizen involvement. Participatory citizenship models are frameworks that outline the criteria by which citizens to belong and participate in a society. This review aimed to identify how participatory citizenship is enabled through co-production.
METHODS: A systematic review was conducted of studies in which a participatory citizenship model informed co-production strategies in health research.
FINDINGS: Of 215 unique articles, 13 articles met the inclusion criteria and were included in the synthesis. Four aspects characteristic of how participatory citizenship models inform co-production in health research were identified. These were, Aspect (1) Co-production enables diverse citizens to participate in health research; Aspect (2) Citizens' lived-experience contextualises and shapes all stages of the health research process; Aspect (3) Co-production shares power and ownership between citizens and research teams; and, Aspect (4) Co-production through health research enables citizens to actively participate in the development of their communities. The first three aspects enable the fourth aspect to be fully enacted within a research project.
CONCLUSION: Citizenship-informed co-production ensures research enables local citizens to apply their lived-experience and local knowledge to shape community health and is valuable to policymakers and practitioners working to reduce health inequalities. Researchers are encouraged to engage with these four aspects through authentic co-production. The authors present a set of recommendations for researchers based on the findings of the synthesis.

Keywords:  citizenship; co‐production; health inequalities; patient and public participation; public involvement; systematic review; values

DOI:  https://doi.org/10.1111/hex.70394
Curr Med Res Opin. 2025 Aug 25. 1-15

Patient involvement in publications: qualitative mapping of the current landscape within the pharmaceutical industry.

Adeline Rosenberg, Liz Clark, Graham R McClelland.

   OBJECTIVE: Patient involvement in pharmaceutical industry-sponsored publications is a rapidly evolving practice. It is supported by industry guidelines, but currently inconsistent across organizations. This study aimed to qualitatively map the landscape of current practices and gaps in patient involvement in peer-reviewed journal publications of pharmaceutical industry-sponsored research, and to define the specific roles and activities in which patients are involved.
METHODS: This qualitative, patient-led study was conducted using semi-structured interviews with purposively sampled experts in patient engagement and publications, including patients. Interviews were conducted online, transcribed, and thematically analysed. Landscape elements were visually mapped, and themes were generated through an inductive and experientially situated thematic analysis.
RESULTS: Interviews were conducted with 20 participants recruited globally, with a majority from the United Kingdom. Participants represented diverse stakeholder categories and reported patient involvement across all stages and aspects of the publication lifecycle, with patients both as external consultants and as professionals working within the system. Five overarching themes and 20 sub-themes were identified, including: patient identities and roles; principles and values; processes and practices; variations over time and across organizations; and impact. Significant gaps were identified in consistency, quality, and scale, for example including gaps in infrastructure barriers and diversity.
CONCLUSIONS: Patient involvement in pharmaceutical publications is actively happening across the publication lifecycle and is rapidly growing and evolving. This study provides an evidence base via a qualitative mapping of the experiential landscape and highlights the need for established best practices to support consistency and quality in meaningful patient involvement in publications.

Keywords:  GRIPP2; Patient engagement; patient and public involvement; patient authorship; publication practices

DOI:  https://doi.org/10.1080/03007995.2025.2545496
Front Health Serv. 2025 ;5 1624820

Empowering partnership: key lessons from the co-development of patient-oriented research with parents, researchers, and healthcare professionals.

Jacqueline M Wilson, Seija K Kromm, Christine Johns, Michelle L Neraasen, Tapuwa Chinhengo, Shannon D Anderson, Elsa Fiedrich, Deborah McNeil.

   Background: Co-developing research in partnership with patients and families is integral to Learning Health Systems (LHSs). These partnerships advance LHS objectives by (1) ensuring innovation is relevant to local contexts, (2) accelerating evidence into practice, and (3) improving services and outcomes that are meaningful to patients and families. Despite the importance of patient and family engagement in LHSs, strategies that guide researchers to build and sustain teams of patients, clinicians, and other partners are under-reported.
Objective: We report actionable insights for co-developing research learned through our experience within Alberta's LHS.
Context: Parents from a provincial advisory group in Alberta identified the need to evaluate parents' experiences with family-centered care in Neonatal Intensive Care Units (NICUs). In response, a research team of parent partners, researchers, and clinicians is co-developing a validated experience measure for parents in NICUs.
Methods: During co-development, the research team engaged in reflective practice through semi-structured discussion informed by Schön's Reflection Model. Notes from the discussion were thematically analyzed to identify insights and research co-development strategies.
Results: Three key insights and associated strategies were generated: (1) operationalizing co-development through a shared governance structure, terms of reference, and dedicated reflection; (2) adaptive approaches to team member involvement, renegotiating workflows, and addressing dissent; and (3) team evolution by nurturing reciprocity and utilizing existing partnerships to recruit members.
Conclusion: We demonstrate how a team of patient partners, researchers, and clinicians can effectively co-develop research to address health system issues, and we present strategies to support patient-oriented research teams within LHSs.

Keywords:  co-developed research; knowledge translation; patient and public involvement; patient engagement; patient- and family-centered care; patient-oriented research

DOI:  https://doi.org/10.3389/frhs.2025.1624820