bims-curels Biomed News
on Leigh syndrome
Issue of 2023–04–23
three papers selected by
Cure Mito Foundation



  1. Elife. 2023 Apr 19. pii: e87194. [Epub ahead of print]12
      A large-scale study of mutations in mitochondrial DNA has revealed a subset that do not accumulate with age.
    Keywords:  aging; duplex sequencing; genetics; genomics; mitochondrial DNA; mouse; somatic mutations
    DOI:  https://doi.org/10.7554/eLife.87194
  2. Dis Model Mech. 2023 Apr 01. pii: dmm049783. [Epub ahead of print]16(4):
      The list of mitochondrial DNA (mtDNA) variants detected in individuals with neurodegenerative diseases is constantly growing. Evaluating their functional consequences and pathogenicity is not easy, especially when they are found in only a limited number of patients together with wild-type mtDNA (heteroplasmy). Owing to its amenability to mitochondrial genetic transformation and incapacity to stably maintain heteroplasmy, and the strong evolutionary conservation of the proteins encoded in mitochondria, Saccharomyces cerevisiae provides a convenient model to investigate the functional consequences of human mtDNA variants. We herein report the construction and energy-transducing properties of yeast models of eight MT-ATP6 gene variants identified in patients with various disorders: m.8843T>C, m.8950G>A, m.9016A>G, m.9025G>A, m.9029A>G, m.9058A>G, m.9139G>A and m.9160T>C. Significant defect in growth dependent on respiration and deficits in ATP production were observed in yeast models of m.8950G>A, m.9025G>A and m.9029A>G, providing evidence of pathogenicity for these variants. Yeast models of the five other variants showed very mild, if any, effect on mitochondrial function, suggesting that the variants do not have, at least alone, the potential to compromise human health.
    Keywords:   MT-ATP6 ; ATP synthase; LHON; MILS; Mitochondrial DNA mutation; Mitochondrial diseases; Yeast; mtDNA
    DOI:  https://doi.org/10.1242/dmm.049783
  3. Orphanet J Rare Dis. 2023 Apr 17. 18(1): 84
       BACKGROUND: The diversity of patient experiences of orphan drug development has until recently been overlooked, with the existing literature reporting the experience of some patients and not others. The current evidence base (the best available current research) is dominated by quantitative surveys and patient reported outcome measures defined by researchers. Where research that uses qualitative methods of data collection and analysis has been conducted, patient experiences have been studied using content analysis and automatic textual analysis, rather than in-depth qualitative analytical methods. Systematic reviews of patient engagement in orphan drug development have also excluded qualitative studies. The aim of this paper is to review qualitative literature about how patients and other members of the public engage with orphan drug development.
    METHODS: We conducted a systematic search of qualitative papers describing a range of patient engagement practices and experiences were identified and screened. Included papers were appraised using a validated tool (CASP), supplemented by reporting guidance (COREQ), by two independent researchers.
    RESULTS: 262 papers were identified. Thirteen papers reported a range of methods of qualitative data collection. Many conflated patient and public involvement and engagement (PPIE) with qualitative research. Patients were typically recruited via their physician or patient organisations. We identified an absence of overarching philosophical or methodological frameworks, limited details of informed consent processes, and an absence of recognisable methods of data analysis. Our narrative synthesis suggests that patients and caregivers need to be involved in all aspects of trial design, including the selection of clinical endpoints that capture a wider range of outcomes, the identification of means to widen access to trial participation, the development of patient facing materials to optimise their decision making, and patients included in the dissemination of trial results.
    CONCLUSIONS: This narrative qualitative synthesis identified the explicit need for methodological rigour in research with patients with rare diseases (e.g. appropriate and innovative use of qualitative methods or PPIE, rather than their conflation); strenuous efforts to capture the perspectives of under-served, under-researched or seldom listened to communities with experience of rare diseases (e.g. creative recruitment and wider adoption of post-colonial practices); and a re-alignment of the research agenda (e.g. the use of co-design to enable patients to set the agenda, rather than respond to what they are being offered).
    Keywords:  Orphan drugs; Patient engagement; Patient involvement; Qualitative research; Rare diseases; Systematic review
    DOI:  https://doi.org/10.1186/s13023-023-02682-w