bims-curels Biomed News
on Leigh syndrome
Issue of 2023‒09‒17
twelve papers selected by
Cure Mito Foundation

  1. Res Involv Engagem. 2023 Sep 09. 9(1): 80
      BACKGROUND: Patient engagement in research refers to collaboration between researchers and patients (i.e., individuals with lived experience including informal caregivers) in developing or conducting research. Offering non-financial (e.g., co-authorship, gift) or financial (e.g., honoraria, salary) compensation to patient partners can demonstrate appreciation for patient partner time and effort. However, little is known about how patient partners are currently compensated for their engagement in research. We sought to assess the prevalence of reporting patient partner compensation, specific compensation practices (non-financial and financial) reported, and identify benefits, challenges, barriers and enablers to offering financial compensation.METHODS: We conducted a systematic review of studies citing the Guidance for Reporting the Involvement of Patients and the Public (GRIPP I and II) reporting checklists (October 2021) within Web of Science and Scopus. Studies that engaged patients as research partners were eligible. Two independent reviewers screened full texts and extracted data from included studies using a standardized data abstraction form. Data pertaining to compensation methods (financial and non-financial) and reported barriers and enablers to financially compensating patient partners were extracted. No formal quality assessment was conducted since the aim of the review is to describe the scope of patient partner compensation. Quantitative data were presented descriptively, and qualitative data were thematically analysed.
    RESULTS: The search identified 843 studies of which 316 studies were eligible. Of the 316 studies, 91% (n = 288) reported offering a type of compensation to patient partners. The most common method of non-financial compensation reported was informal acknowledgement on research outputs (65%, n = 206) and co-authorship (49%, n = 156). Seventy-nine studies (25%) reported offering financial compensation (i.e., honoraria, salary), 32 (10%) reported offering no financial compensation, and 205 (65%) studies did not report on financial compensation. Two key barriers were lack of funding to support compensation and absence of institutional policy or guidance. Two frequently reported enablers were considering financial compensation when developing the project budget and adequate project funding.
    CONCLUSIONS: In a cohort of published studies reporting patient engagement in research, most offered non-financial methods of compensation to patient partners. Researchers may need guidance and support to overcome barriers to offering financial compensation.
    Keywords:  Financial compensation; Patient engagement; Patient partner; Recognition
  2. Endocr Metab Immune Disord Drug Targets. 2023 Sep 14.
      INTRODUCTION: Mitochondrial diseases are rare, heterogeneous, incurable and complex to diagnose. Probably due to their rareness, there is still a lack of literacy in this area, especially in society, but also in schools and in general, health care services. Accordingly, tools that may bring advancement in science and health literacy are needed. Mit.OnOff is a science communication project based on a bilateral partnership between the University of Coimbra (Portugal) and the University of Bergen (Norway). It aims to inform society about rare diseases related to mitochondrial cytopathies with an emphasis on LHON.METHODS: The initiative focuses on the creation of an illustrated book explaining the diseases caused by the failure of energy production in simple and accessible language. The aim is to raise awareness (particularly in Portugal and Norway) and provide in-depth knowledge to people suffering from these diseases.
    RESULTS/CASE REPORT: This project involves expert scientists in the field of mitochondrial disease, science communicators and artists in alignment with the United Nations SDGs, Agenda 2030. Mit.OnOff is a bilateral partnership (Portugal and Norway) established to address the lack of knowledge and health literacy on the subject of mitochondrial disease. The book will be distributed in both countries, creating a sense of inclusion and visibility and influencing decisions regarding these diseases. It is a relevant educational medium (e.g., schools, health care provision). The distribution of the book is complemented with other communication materials. Oral communications are made, together with public involvement, in which special glasses will be distributed to simulate a mitochondrial disease that leads to blindness (LHON) for the public to experience what it is like living with a rare disease.
    CONCLUSION: It is hoped that the production of this book will give patients a sense of inclusion and representation in the media. This, in turn, will contribute to achieving the SDG targets (3,4,5,8,10,12), i.e., ensuring people live healthy lives, reducing child mortality, and increasing life expectancy, ensuring access to inclusive, equitable and quality education for all, ensuring gender equality, and contributing to a peaceful and prosperous world.
    Keywords:  LHON; health literacy; mitochondria; mitochondrial cytopathies; mitochondrial diseases; rare diseases; science communication
  3. Case Rep Psychiatry. 2023 ;2023 8886555
      Introduction: Leigh syndrome (LS) is a mitochondrial disease characterized by subacute necrotizing encephalomyelopathy with an estimated incidence of 1:40,000 births. The comorbidity of psychotic symptoms noted in mitochondrial and psychiatric diseases has spurred interest in the effects of DNA mutations and psychiatric disorders. Case presentation. We report the case of a Tunisian 28-year-old male diagnosed with maternally inherited Leigh syndrome. He presented anxiety and auditory hallucinations, and he reported a vague, unsystematized delusion evolving since 6 months. Significant remission was observed at risperidone 3 mg/day. Discussion. The normality of explorations in our case raised the issue of the link between the two diseases, supporting the hypothesis that mitochondrial dysfunction maybe the primary origin of psychotic disorders.Conclusion: The aim of our work is to study the relations between mitochondrial dysfunction and psychiatric symptoms. Further study of mitochondrial dysfunction in psychiatric disorders is expected to be useful for the development of cellular disease markers and new psychotropics.
  4. JIMD Rep. 2023 Sep;64(5): 375-386
      Single large-scale mitochondrial deletion syndromes (SLSMDS) are ultra-rare, progressive multi-system diseases that make children largely dependent on their caregivers for both medical and non-medical needs. Yet, few studies have examined the burden felt among caregivers. As part of a larger research study, 42 caregivers of children with SLSMDS completed two surveys to assess caregiver burden. The Mitochondrial Care Network Patient Needs Survey (MCN-PNS) is a novel assessment that examines the logistical, time, and financial costs experienced by caregivers of children with SLSMDS. The Zarit Burden Interview (ZBI-22) is a validated assessment that examines caregivers' psychological health. Results demonstrate the unique burden experienced by caregivers of children with SLSMDS. One notable finding was the high psychological burden. Nearly 90% of caregivers experience psychological burden, with 20% of caregivers at risk for anxiety and depression. Caregivers were primarily concerned about what the future held for their child. Additional burdens included the time required to coordinate the child's healthcare visits and financial strains. Caregivers reported minimal delays in establishing care with a mitochondrial care specialist and felt confident in their understanding of their child's disease and treatment(s). Overall, there is a need for expanded logistical, financial, and psychological support from mitochondrial disease centers and advocacy groups for caregivers of children with SLSMDS.
    Keywords:  Kearns Sayre syndrome; Pearson syndrome; caregiver burden; mtDNA; rare disease registry; single large‐scale mitochondrial deletion syndromes
  5. Orphanet J Rare Dis. 2023 Sep 11. 18(1): 285
      Necessity driven organisational change in the post-pandemic landscape has seen health care providers adopting innovations to manage and process health data. These include the use of 'real-world' datasets of routinely collected clinical information, enabling data-driven delivery. Rare disease risks being 'left-behind' unless our clinical and research communities engage with the challenges and opportunities afforded by the burgeoning field of health data informatics. We address the challenges to the meaningful use and reuse of rare disease data, and, through a series of recommendations around workforce education, harmonisation of taxonomy, and ensuring an inclusive health data environment, we highlight the role that those who manage rare disease must play in addressing them.
    Keywords:  Biomedical; Electronic health records; Epidemiology; Information management; Rare disease; Translational research
  6. Neurobiol Dis. 2023 Sep 11. pii: S0969-9961(23)00303-0. [Epub ahead of print] 106288
      Mutations in the NADH dehydrogenase (ubiquinone reductase) iron‑sulfur protein 4 (NDUFS4) gene, which encodes for a key structural subunit of the OXFOS complex I (CI), lead to the most common form of mitochondrial disease in children known as Leigh syndrome (LS). As in other mitochondrial diseases, epileptic seizures constitute one of the most significant clinical features of LS. These seizures are often very difficult to treat and are a sign of poor disease prognosis. Mice with whole-body Ndufs4 KO are a well-validated model of LS; they exhibit epilepsy and several other clinical features of LS. We have previously shown that mice with Ndufs4 KO in only GABAergic interneurons (Gad2-Ndufs4-KO) reproduce the severe epilepsy phenotype observed in the global KO mice. This observation indicated that these mice represent an excellent model of LS epilepsy isolated from other clinical manifestations of the disease. To further characterize this epilepsy phenotype, we investigated seizure susceptibility to selected exogenous seizure triggers in Gad2-Ndufs4-KO mice. Then, using electrophysiology, imaging, and immunohistochemistry, we studied the cellular, physiological, and neuroanatomical consequences of Ndufs4 KO in GABAergic interneurons. Homozygous KO of Ndufs4 in GABAergic interneurons leads to a prominent susceptibility to exogenous seizure triggers, impaired interneuron excitability and interneuron loss. Finally, we found that the hippocampus and cortex participate in the generation of seizure activity in Gad2-Ndufs4-KO mice. These findings further define the LS epilepsy phenotype and provide important insights into the cellular mechanisms underlying epilepsy in LS and other mitochondrial diseases.
    Keywords:  Epilepsy; Excitability; GABAergic interneuron; Ndufs4; Seizures; hippocampus
  7. Neurohospitalist. 2023 Oct;13(4): 448-449
    Keywords:  Cognitive impairment ; Epilepsy; MELAS; Mitochondrial disease; Seizures; Stroke and Cerebrovascular Disease
  8. Br J Anaesth. 2023 Sep 07. pii: S0007-0912(23)00438-5. [Epub ahead of print]
    Keywords:  neuropathic pain; pain management; patient and public involvement; patient autonomy; shared decision-making
  9. Hum Gene Ther. 2023 Sep 11.
      The development of viral vectors and recombinant DNA technology since the 1960s has enabled gene therapy to become a real therapeutic option for several inherited and acquired diseases. After several ups and downs in the gene therapy field, we are currently living a new era in the history of medicine in which several ex vivo and in vivo gene therapies have reached maturity. This is testified by the recent marketing authorization of several gene therapy medicinal products. Additionally, many others are currently under evaluation after exhaustive investigation in human clinical trials. In this review we summarize some of the most significant milestones in the development of gene therapy medicinal products that have already facilitated the treatment of significant number of rare diseases. Despite progresses in the gene therapy field, the transfer of these innovative therapies to the clinical practice is also finding important restrictions. Advances and also challenges in the progress of gene therapy for rare diseases are discussed in this opening review of a Human Gene Therapy issue dedicated to the 30th annual Congress of the European Society for Gene and Cell Therapy.
  10. Front Neurol. 2023 ;14 1239664
      Background: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is a group of maternally inherited disorders caused by mutations or deletions in mitochondrial genes with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes as the main clinical manifestations.Case presentation: We reported a 20-year-old female patient with MELAS syndrome combined with autoimmune abnormalities. She suffered from an intermittent headache in the right temporal region with no obvious cause, and then, after strenuous exercise in dance class, the headache became aggravated, accompanied by unresponsiveness, blurred vision, and diplopia. Her blood lactate levels were elevated, her antinuclear antibodies were positive, and the antimetabolic glutamate receptors 5 in her serum were positive. Brain DWI showed a hypertensive signal in the right temporo-parietal-occipital cortex and subcortical area. Brain MRS showed decreased NAA peak and increased Lac peak. Muscle biopsy showed myogenic damage, and the modified Gomori trichrome (MGT) staining showed ragged red fibers (RRF). A genetic study revealed a mitochondrial DNA A3243G mutation.
    Conclusion: Mitochondrial encephalomyopathy is a rare clinical condition; however, the association with autoimmune diseases is not yet clear and still needs further research and analysis.
    Keywords:  MELAS; antimetabolic glutamate receptor 5 encephalitis; antinuclear antibodies (ANA); autoimmune abnormalities; mitochondrial encephalomyopathy
  11. Health Expect. 2023 Sep 13.
    CanGene-CanVar Patient Reference Panel
      INTRODUCTION: Patient decision aids (PtDA) complement shared decision-making with healthcare professionals and improve decision quality. However, PtDA often lack theoretical underpinning. We are codesigning a PtDA to help people with increased genetic cancer risks manage choices. The aim of an innovative workshop described here was to engage with the people who will use the PtDA regarding the theoretical underpinning and logic model outlining our hypothesis of how the PtDA would lead to more informed decision-making.METHODS: Short presentations about psychological and behavioural theories by an expert were interspersed with facilitated, small-group discussions led by patients. Patients were asked what is important to them when they make health decisions, what theoretical constructs are most meaningful and how this should be applied to codesign of a PtDA. An artist created a visual summary. Notes from patient discussions and the artwork were analysed using reflexive thematic analysis.
    RESULTS: The overarching theme was: It's personal. Contextual factors important for decision-making were varied and changed over time. There was no one 'best fit' theory to target support needs in a PtDA, suggesting an inductive, flexible framework approach to programme theory would be most effective. The PtDA logic model was revised based on patient feedback.
    CONCLUSION: Meaningful codesign of PtDA including discussions about the theoretical mechanisms through which they support decision-making has the potential to lead to improved patient care through understanding the intricately personal nature of health decisions, and tailoring content and format for holistic care.
    PATIENT CONTRIBUTION: Patients with lived experience were involved in codesign and coproduction of this workshop and analysis as partners and coauthors. Patient discussions were the primary data source. Facilitators provided a semi-structured guide, but they did not influence the patient discussions or provide clinical advice. The premise of this workshop was to prioritise the importance of patient lived experience: to listen, learn, then reflect together to understand and propose ideas to improve patient care through codesign of a PtDA.
    Keywords:  codesign; coproduction; patient decision aid; shared decision-making