bims-curels Biomed News
on Leigh syndrome
Issue of 2023‒08‒20
nine papers selected by
Cure Mito Foundation

  1. EMBO Rep. 2023 Aug 17. e54540
      Mitochondrial replacement technology (MRT) aims to reduce the risk of serious disease in children born to women who carry pathogenic mitochondrial DNA (mtDNA) variants. By transplanting nuclear genomes from eggs of an affected woman to enucleated eggs from an unaffected donor, MRT creates new combinations of nuclear and mtDNA. Based on sets of shared sequence variants, mtDNA is classified into ~30 haplogroups. Haplogroup matching between egg donors and women undergoing MRT has been proposed as a means of reducing mtDNA sequence divergence between them. Here we investigate the potential effect of mtDNA haplogroup matching on clinical delivery of MRT and on mtDNA sequence divergence between donor/recipient pairs. Our findings indicate that haplogroup matching would limit the availability of egg donors such that women belonging to rare haplogroups may have to wait > 4 years for treatment. Moreover, we find that intra-haplogroup sequence variation is frequently within the range observed between randomly matched mtDNA pairs. We conclude that haplogroup matching would restrict the availability of MRT, without necessarily reducing mtDNA sequence divergence between donor/recipient pairs.
    Keywords:  haplogroup matching; mitochondrial disease; mitochondrial replacement therapy
  2. Qual Health Res. 2023 Aug 14. 10497323231192379
      The demand for patient-centred care and patient engagement in their healthcare has driven patient portal introduction. The widespread adoption and use of patient portals, however, has been a rather slow process in the United Kingdom. Hence, a limited number of studies have explored patient perceptions and experiences of general portal use, which forms a foundation for successful implementation of a portal. This study, therefore, focuses on the experiences and attitudes of patients regarding use of patient portals and access to their health information. It further explores various factors perceived by patients that may influence portal use and uptake. The overall findings from this study highlight positive patient perceptions of portal use. Nevertheless, it demonstrates various areas of improvement essential to ensure future success of portal implementation and acceptance.
    Keywords:  health information; patient experience; patient portal; qualitative; user perceptions
  3. FASEB J. 2023 09;37(9): e23139
      Mutations in POLG, the gene encoding the catalytic subunit of the mitochondrial DNA (mtDNA) polymerase gamma (Pol-γ), lead to diseases driven by defective mtDNA maintenance. Despite being the most prevalent cause of mitochondrial disease, treatments for POLG-related disorders remain elusive. In this study, we used POLG patient-induced pluripotent stem cell (iPSC)-derived neural stem cells (iNSCs), one homozygous for the POLG mutation c.2243G>C and one compound heterozygous with c.2243G>C and c.1399G>A, and treated these iNSCs with ethidium bromide (EtBr) to study the rate of depletion and repopulation of mtDNA. In addition, we investigated the effect of deoxyribonucleoside (dNs) supplementation on mtDNA maintenance during EtBr treatment and post-treatment repopulation in the same cells. EtBr-induced mtDNA depletion occurred at a similar rate in both patient and control iNSCs, however, restoration of mtDNA levels was significantly delayed in iNSCs carrying the compound heterozygous POLG mutations. In contrast, iNSC with the homozygous POLG mutation recovered their mtDNA at a rate similar to controls. When we treated cells with dNs, we found that this reduced EtBr-induced mtDNA depletion and significantly increased repopulation rates in both patient iNSCs. These observations are consistent with the hypothesis that mutations in POLG impair mtDNA repopulation also within intact neural lineage cells and suggest that those with compound heterozygous mutation have a more severe defect of mtDNA synthesis. Our findings further highlight the potential for dNs to improve mtDNA replication in the presence of POLG mutations, suggesting that this may offer a new therapeutic modality for mitochondrial diseases caused by disturbed mtDNA homeostasis.
    Keywords:  deoxynucleosides; iPSCs; mitochondrial DNA replication; neural stem cells; polymerase γ; therapy
  4. Obstet Gynecol Surv. 2023 Aug;78(7): 483-489
      Importance: Genetic carrier screening is performed to identify carriers of rare genetic diseases. Identification of carriers allows patients to make informed reproductive health choices and can decrease the incidence of genetic disorders with serious medical implications.Objective: This review aims to provide an overview of the history of prenatal genetic screening and the various forms of carrier screening, a synopsis of recent changes in society recommendations and current practice guidelines, and discussion of clinical challenges associated with carrier screening.
    Evidence Acquisition: Published practice guidelines from relevant professional societies were reviewed and synthesized. PubMed search was performed for relevant history and clinical considerations of carrier screening.
    Results: Information and evidence summarized in this review include professional society practice guidelines, review articles, and peer-reviewed research articles.
    Conclusions and Relevance: Current practice guidelines differ between stakeholder professional organizations. Expanded carrier screening offers increased identification of rare disease carriers allowing for more informed reproductive choices. However, there are several barriers to the implementation of expanded carrier screening for all patients.
  5. Pharmacoeconomics. 2023 Aug 18.
      BACKGROUND AND OBJECTIVES: Rare diseases have a significant impact on patients, families, the health system, and society. Measuring the socioeconomic burden is crucial to valuing interventions for rare diseases. Healthcare system costs are significant, but so are costs to other government sectors, patients, families, and society. To understand the breadth of costs captured in rare disease studies, we examined the cost categories and elements of socioeconomic burden captured in published studies.METHODS: A scoping review was conducted using five electronic databases to identify English language economic evaluations and cost-of-illness studies of interventions for rare diseases (2011-21). We mapped costs using a previously developed evidence-informed framework of socioeconomic burden costs for rare disease.
    RESULTS: Of 4890 studies identified, 48 economic evaluations and 22 cost-of-illness studies were included. While 18/22 cost-of-illness studies utilized a societal perspective, only 7/48 economic evaluations incorporated societal costs. Most reported cost categories related to medical costs, with medication and hospitalizations being the most common elements for both study designs. Costs borne by patients, families, and society were reported less among economic evaluations than cost-of-illness studies. These included: productivity (10% vs 77%), travel/accommodation (6% vs 68%), government benefits (4% vs 18%), and family impacts (0% vs 50%).
    CONCLUSIONS: Contrary to cost-of-illness analyses, most of the included economic evaluations did not account for the hidden burden of rare diseases, that is, costs borne by patients, families, and societies. Including these types of costs in future studies would provide a more comprehensive picture of the burden of disease, providing empirical data to inform how we value and make decisions regarding rare disease interventions, health policy, and resource allocation.
  6. J Mark Access Health Policy. 2023 ;11(1): 2239557
      Background: The benefits of preventive interventions lack comprehensive evaluation in standard health technology assessments (HTA), particularly for rare and transmissible diseases. Objective: To identify possible considerations for future HTA using analogies between the treatment and prevention of rare diseases. Study design: An Expert panel meeting assessed whether one HTA assessment framework can be applied to assess both rare disease treatments and preventive interventions. Experts also evaluated the range of value elements currently included in HTAs and their applicability to rare, transmissible, and/or preventable diseases. Results: A broad range of value should be considered when assessing rare, transmissible disease prevention. Although standard HTA can be applied to transmissible diseases, the risk of local outbreaks and the need for large-scale prevention programs suggest a modified assessment framework, capable of incorporating prevention-specific value elements in HTAs. A 'Rule of Prevention' framework was proposed to allow broader value considerations anchored to severity, equity, and prevention benefits in decision-making for preventive interventions for rare transmissible diseases. Conclusion: The proposed prevention framework introduces an explicit initial approach to consistently assess rare transmissible diseases, and to incorporate the broader value of preventive interventions compared with treatment.
    Keywords:  Prevention; assessment; rare disease; vaccination; value
  7. J Genet Genomics. 2023 Aug 14. pii: S1673-8527(23)00164-9. [Epub ahead of print]
      Monogenic disorders refer to a group of human diseases caused by mutations in single genes. While disease-modifying therapies have offered some relief to symptoms and delayed progression for some monogenic diseases, most of these diseases still lack effective treatments. In recent decades, gene therapy has emerged as a promising therapeutic strategy for genetic disorders. Researchers have developed various gene manipulation tools and gene delivery systems to treat monogenic diseases. Despite this progress, concerns about inefficient delivery, persistent expression, immunogenicity, toxicity, capacity limitation, genomic integration, and limited tissue specificity still need to be addressed. This review gives an overview of commonly used gene therapy and delivery tools, along with the challenges they face and the potential strategies to counter them.
    Keywords:  Challenges; Gene delivery; Gene editing; Gene therapy; Monogenic diseases
  8. Res Involv Engagem. 2023 Aug 14. 9(1): 66
      PURPOSE: Although medical research dissemination is intended to benefit members of society, few members of society actually participate in the process of publishing findings. This study shares findings from community members' (including patients and the public) experiences being trained as medical journal reviewers.METHODS: We analyzed findings from two focus group interviews of community reviewers (N = 29) to identify themes in their experiences with the training program.
    RESULTS: Community members trained as journal reviewers appreciated learning the context under which manuscript development and review occur from authors and funders, the value of the community member perspectives to science, and strengthened their critical thinking skills. A range of training tools and strategies included glossaries of research terms, creating review guides, practicing reviews, being trained by a supportive team, and working with and learning collaboratively.
    CONCLUSIONS: Training as a journal reviewer has a positive impact on participating community members. Programs training community members as journal reviewers should incorporate guest speakers well-versed in community engaged research, group activities, a variety of training tools and materials, and highly supportive training teams.
    Keywords:  Case study; Community engaged research; Medical research; Patient and public involvement; Research dissemination