bims-curels Biomed News
on Leigh syndrome
Issue of 2024–11–10
sixteen papers selected by
Cure Mito Foundation
  1. Phase 2b program with sonlicromanol in patients with mitochondrial disease due to m.3243A>G mutation.
  2. Auditory and vestibular function in mitochondrial patients harbouring the m.3243A>G variant.
  3. Embedding patient engagement in the R&D process of a life sciences company through co-creation with a patient expert R&D board: a case study.
  4. The quality and detection limits of mitochondrial heteroplasmy by long read nanopore sequencing.
  5. Balancing Anesthesia in a Child With Mitochondrial Disease: A Case Report.
  6. Building on the successes of patient-focused drug development: a call for new policies to maintain momentum.
  7. Mitochondria in skeletal system-related diseases.
  8. Hope for rare diseases.
  9. Prognostic impact of donor mitochondrial genomic variants in myelodysplastic neoplasms after stem-cell transplantation.
  10. The role of mitochondrial transfer in the suppression of CD8+ T cell responses by Mesenchymal stem cells.
  11. High frequency of mitochondrial DNA rearrangements in the peripheral blood of adults with intellectual disability.
  12. Patient and public involvement in the design of an international clinical trial: real world experience.
  13. Being the other child - A systematic review on the quality of life and mental health of siblings of children with rare diseases.
  14. Perspective targeted diagnosis and therapy of mitochondrial bioenergetics across different diagnoses.
  15. Mitochondrial nucleoids.
  16. You don't have celiac disease: a patient perspective on potential issues with stress leading to misdiagnosis.
  1. Brain. 2024 Nov 06. pii: awae277. [Epub ahead of print]
    Phase 2b program with sonlicromanol in patients with mitochondrial disease due to m.3243A>G mutation.
    Jan Smeitink, Just van Es, Brigitte Bosman, Mirian C H Janssen, Thomas Klopstock, Grainne Gorman, John Vissing, Gerrit Ruiterkamp, Chris J Edgar, Evertine J Abbink, Rob van Maanen, Oksana Pogoryelova, Claudia Stendel, Almut Bischoff, Ivan Karin, Mahtab Munshi, Anne Kümmel, Lydia Burgert, Christianne Verhaak, Herma Renkema.
      Mitochondrial disease is a group of rare conditions, with no approved treatment to date, except for Leber hereditary optic neuropathy. Therapeutic options to alleviate the symptoms of mitochondrial disease are urgently needed. Sonlicromanol is a promising candidate, as it positively alters the key metabolic and inflammatory pathways associated with mitochondrial disease. Sonlicromanol is a reductive and oxidative distress modulator, selectively inhibiting microsomal prostaglandin E1 synthase activity. This Phase 2b program, aiming at evaluating sonlicromanol in adults with m.3243A>G mutation and primary mitochondrial disease, consisted of a randomized controlled (RCT) study (dose-selection) followed by a 52-week open-label extension study (EXT, long-term tolerability, safety, and efficacy of sonlicromanol). Patients were randomized (1:1:1) to receive 100- or 50-mg sonlicromanol, or placebo twice daily (bid) for 28 days with ≥2-week wash-out period between treatments. Patients who completed the RCT study entered the EXT study wherein they received 100-mg sonlicromanol bid. Overall, 27 patients were randomized (24 RCT patients completed all periods). 15 patients entered the EXT, and 12 patients were included in the EXT analysis set. All patients reported good tolerability and favourable safety, with pharmacokinetic results comparable to the earlier Phase 2a study. The RCT primary endpoint (change from placebo in the attentional domain of cognition score [IDN: visual identification, Cogstate]) did not reach statistical significance. Using a categorisation of the subject's period baseline a treatment effect over placebo was observed if their baseline was more affected (p=0.0338). Using this approach, there were signals of improvements over placebo in at least one dose in the Beck Depression Inventory (BDI, p=0.0143), Cognitive Failure Questionnaire (CFQ, p=0.0113), and the Depression subscale of the Hospital Anxiety and Depression Scale (p=0.0256). Statistically and/or clinically meaningful improvements were observed in the patient- and clinician-reported outcome measures at the end of the EXT study (Test of attentional performance [TAP] with alarm, p=0.0102; TAP without alarm, p=0.0047; BDI somatic, p=0.0261; BDI Total, p=0.0563; SF12 physical component score, p=0.0008). Seven of nine domains of RAND-Short form-36 like SF-36 pain improved (p=0.0105). Other promising results were observed in Neuro QoL-Fatigue-SF (p=0.0036), MiniBESTest (p=0.0009), McGill Pain Questionnaire (p=0.0105), EQ-5D-5L-VAS (p=0.0213) and EQ-5D-5L-index (p=0.0173). Most patients showed improvement in the 5× sit-to-stand test. Sonlicromanol was well-tolerated and demonstrated a favourable benefit/risk ratio for up to one year. Sonlicromanol was efficacious in patients when affected at baseline, as seen across a variety of clinically relevant domains. Long-term treatment showed more pronounced changes from baseline.
    Keywords:  MELAS; MIDD; m.3243A>G; primary mitochondrial disease; sonlicromanol
    DOI:  https://doi.org/10.1093/brain/awae277
  2. Brain Commun. 2024 ;6(6): fcae361
    Auditory and vestibular function in mitochondrial patients harbouring the m.3243A>G variant.
    Renae J Stefanetti, Jane Newman, Alasdair P Blain, Donella Chisari, Gráinne S Gorman, Gary Rance.
      Hearing impairment is a frequent clinical feature in patients with mitochondrial disease harbouring the pathogenic variant, m.3243A>G. However, auditory neural dysfunction, its perceptual consequences and implications for patient management are not established. Similarly, the association with vestibular impairment has not yet been explored. This case-control study investigated in 12 adults with genetically confirmed m.3243A>G adults [9 females; 45.5 ± 16.3 years (range 18-66); 47.1 ± 21.5 hearing level, dB] compared with 12 age, sex and hearing level-matched controls with sensory (cochlear level) hearing loss [9 females; 46.6 ± 11.8 years (range 23-59); 47.7 ± 25.4 hearing level, dB]. Participants underwent a battery of electroacoustic, electrophysiologic and perceptual tests, which included pure tone audiometry, otoacoustic emissions, auditory brainstem responses, auditory temporal processing measures, monaural/binaural speech perception, balance and vestibular testing and self-reported questionnaires (dizziness and hearing disability). Our findings showed evidence of auditory neural abnormality and perceptual deficits greater than expected for cochlear pathology. Compared with matched controls with sensory hearing loss, adults with mitochondrial disease harbouring m.3243A>G had abnormal electrophysiologic responses from the VIII nerve and auditory brainstem (P = 0.005), an impaired capacity to encode rapidly occurring acoustic signal changes (P = 0.005), a reduced ability to localize sound sources (P = 0.028) and impaired speech perception in background noise (P = 0.008). Additionally, vestibular dysfunction (P = 0.011), greater perceived dizziness (P = 0.001) and reduced stance time (balance, P = 0.009) were also seen in participants with m.3243A>G mitochondrial disease when compared with matched counterparts. This pilot study revealed that auditory evaluation including evoked potential responses from the auditory nerve/brainstem and speech perception in noise tests should form an important part of the management for individuals with m.3243A>G-related mitochondrial disease. Those presenting with hearing impairment and symptoms concerning balance and dizziness should undergo vestibular testing and appropriate management.
    Keywords:  auditory neuropathy; hearing impairment; m.3243A>G mitochondrial disease; speech perception; vestibular dysfunction
    DOI:  https://doi.org/10.1093/braincomms/fcae361
  3. Res Involv Engagem. 2024 Nov 06. 10(1): 116
    Embedding patient engagement in the R&D process of a life sciences company through co-creation with a patient expert R&D board: a case study.
    Estelle Jobson, Marta Garcia, Danika Sharek, Laura Risueño, Sylvain Arnould, Aude Lemoine-André, Jan Geissler, Ana Amariutei, Sabrina Grigolo, Begonya Nafria Escalera, Thomas Smith, Oriana Sousa, Linda Stone, Janet West.
      Patient involvement is crucial in healthcare, a factor increasingly recognised by life sciences companies and research institutes. This article presents a case study on Servier, a life sciences company that founded a patient expert board, ahead of launching a new research and development (R&D) institute. The aim was to foster a patient-centric culture within the company. The case study explores key developments in patient and public involvement, emphasising a shift from paternalistic to patient-centred approaches, noting few available case studies on patient board collaborations in life sciences. It outlines the evolution of the board, its impact, and practical lessons learned, with related recommendations. The patient board resulted from a three-way collaboration between the company, Patvocates (a patient consultancy), and patient experts recruited. The patient consultancy played a crucial role in project management, governance, and facilitating relationships. The case study provides the context, timeframe, foundations laid, engagement of patient experts, and foundational values, including: co-creation, fair market value remuneration, voluntary participation, and patient-centric meeting protocol. Eighteen patient experts, representing ten disease areas and ten European countries, joined the board and helped prioritise and co-create projects. Ideas for activities were sourced from brainstorming sessions and an in-company challenge. The collaboration yielded five core ideas, each forming a working group. The study describes the groups and their outputs: a patient advisory council, an interactive gallery of patient experience in R&D, patient engagement and entrepreneurship in life sciences, creating patient-focused decentralised trials (DCTs), and staff training on patient engagement. The article emphasises how the organic evolution of the collaboration led to significant insights. Hurdles faced by the company included: upstream planning, cross-company buy-in, compliance, and internal resource allocation. Recommendations for the wider community included: identifying and contracting patient partners; clarifying roles; managing expectations; building trust; logistics; and sustainability. This case study presents a practical, positive example of patient engagement within a life sciences company, offering insights into the establishing, running, and the impact of collaborating with a patient expert board. Lessons learned and recommendations may serve as a model for other companies seeking to engage with patients and evolve towards a more patient-centric approach in their strategies.
    DOI:  https://doi.org/10.1186/s40900-024-00631-w
  4. Sci Rep. 2024 11 05. 14(1): 26778
    The quality and detection limits of mitochondrial heteroplasmy by long read nanopore sequencing.
    Barbara Slapnik, Robert Šket, Klementina Črepinšek, Tine Tesovnik, Barbara Jenko Bizjan, Jernej Kovač.
      This study evaluates long-read and short-read sequencing for mitochondrial DNA (mtDNA) heteroplasmy detection. 592,315 bootstrapped datasets generated from two single-nucleotide mismatched ultra-deep sequenced mtDNA samples were used to assess basecalling error and accuracy, limit of heteroplasmy detection, and heteroplasmy detection across various coverage depths. Results showed high Phred scores of data with GC-rich sequence bias for long reads. Limit of detection of 12% heteroplasmy was identified, showing strong correlation (R2 ≥ 0.955) with expected heteroplasmy but underreporting tendency of high-level variants. Nanopore sequencing shows potential for direct applicability in mitochondrial diseases diagnostics, but stringent validation processes to ensure diagnostic result quality are required.
    Keywords:  Heteroplasmy; Long-read sequencing; Mitochondrial disease; mtDNA
    DOI:  https://doi.org/10.1038/s41598-024-78270-0
  5. Cureus. 2024 Oct;16(10): e70756
    Balancing Anesthesia in a Child With Mitochondrial Disease: A Case Report.
    Akilandeswari Manickam, Kadhij Fathima, Vatsala A Bagri, Abi Vignesh Prabu Ganesh Prabu, Vishnu Priya R.
      Anesthetic management of patients with mitochondrial disease requires an in-depth knowledge and understanding of its pathophysiology to ensure the safe conduct of anesthesia. Our case report illustrates the importance of careful anesthetic planning and execution for a four-year-old undergoing full mouth rehabilitation. It is essential to avoid factors that increase metabolic stress, such as prolonged fasting, hypoglycemia, postoperative nausea, hypothermia, acidosis, hypovolemia, and ischemic or hypoxic events. Balanced general anesthesia was achieved by using incremental doses of anesthetics, narcotics, and muscle relaxants, all selected to minimize any potential impact on mitochondrial function. The perioperative period was uneventful.
    Keywords:  case report; general anaesthesia; mitochondrial disorder; oxidative phosphorylation deficiency type 3; paediatric
    DOI:  https://doi.org/10.7759/cureus.70756
  6. Front Med (Lausanne). 2024 ;11 1416123
    Building on the successes of patient-focused drug development: a call for new policies to maintain momentum.
    Allison Martin, Victoria DiBiaso, Mladen Bozic, Alexander T May.
      Since its commencement as part of the Food and Drug Administration's (FDA) Prescription Drug User Fee Act (PDUFA) V in 2012, patient-focused drug development (PFDD) has become an integral part of the drug development paradigm. FDA encourages the development and use of Patient-Experience Data (PED) as it provides important information on the patients' needs and perspectives and inform regulatory decision-making. While the FDA is required to fill out a table which includes a list of various types of Patient Experience Data (PED) and if such data was reviewed by FDA as part of a drug application, there is still a need to understand how FDA uses PED in its regulatory decision-making. This article examines whether new policies are needed to ensure the full potential of PFDD.
    Keywords:  Food and Drug Administration; PDUFA; benefit–risk; patient experience data; patient-focused drug development; regulatory decision making; regulatory submissions
    DOI:  https://doi.org/10.3389/fmed.2024.1416123
  7. Biomed Pharmacother. 2024 Nov 04. pii: S0753-3322(24)01391-X. [Epub ahead of print]181 117505
    Mitochondria in skeletal system-related diseases.
    Liang Pei, Zhuo Yao, Dong Liang, Keda Yang, Lin Tao.
      Skeletal system-related diseases, such as osteoporosis, arthritis, osteosarcoma and sarcopenia, are becoming major public health concerns. These diseases are characterized by insidious progression, which seriously threatens patients' health and quality of life. Early diagnosis and prevention in high-risk populations can effectively prevent the deterioration of these patients. Mitochondria are essential organelles for maintaining the physiological activity of the skeletal system. Mitochondrial functions include contributing to the energy supply, modulating the Ca2+ concentration, maintaining redox balance and resisting the inflammatory response. They participate in the regulation of cellular behaviors and the responses of osteoblasts, osteoclasts, chondrocytes and myocytes to external stimuli. In this review, we describe the pathogenesis of skeletal system diseases, focusing on mitochondrial function. In addition to osteosarcoma, a characteristic of which is active mitochondrial metabolism, mitochondrial damage occurs during the development of other diseases. Impairment of mitochondria leads to an imbalance in osteogenesis and osteoclastogenesis in osteoporosis, cartilage degeneration and inflammatory infiltration in arthritis, and muscle atrophy and excitationcontraction coupling blockade in sarcopenia. Overactive mitochondrial metabolism promotes the proliferation and migration of osteosarcoma cells. The copy number of mitochondrial DNA and mitochondria-derived peptides can be potential biomarkers for the diagnosis of these disorders. High-risk factor detection combined with mitochondrial component detection contributes to the early detection of these diseases. Targeted mitochondrial intervention is an effective method for treating these patients. We analyzed skeletal system-related diseases from the perspective of mitochondria and provided new insights for their diagnosis, prevention and treatment by demonstrating the relationship between mitochondria and the skeletal system.
    Keywords:  Mitochondria; Mitophagy; ROS; Skeletal system; TCA
    DOI:  https://doi.org/10.1016/j.biopha.2024.117505
  8. Lancet. 2024 Nov 02. pii: S0140-6736(24)02414-0. [Epub ahead of print]404(10464): 1701
    Hope for rare diseases.
    The Lancet.
      
    DOI:  https://doi.org/10.1016/S0140-6736(24)02414-0
  9. J Hematol Oncol. 2024 Nov 04. 17(1): 104
    Prognostic impact of donor mitochondrial genomic variants in myelodysplastic neoplasms after stem-cell transplantation.
    Jing Dong, Shahram Arsang-Jang, Tao Zhang, Zhongyuan Chen, Yung-Tsi Bolon, Stephen Spellman, Raul Urrutia, Paul Auer, Wael Saber.
      Mitochondrial DNA (mtDNA) variants in patients with myelodysplastic neoplasms (MDS) are shown to be prognostic of outcomes after allogeneic hematopoietic cell transplantation (allo-HCT). However, the prognostic impact of donor mtDNA variants is unknown. Here, we performed whole-genome sequencing on 494 donors who were matched to MDS patients enrolled in the Center for International Blood and Marrow Transplant Research (CIBMTR). We evaluated the impact of donor mtDNA variants on recipients' transplantation outcomes, including overall survival, relapse, relapse-free survival, and transplant-related mortality. The optimism-adjusted bootstrap method was employed to evaluate the prognostic performance of models that include donor mtDNA variants alone and combined with MDS- and HCT-related clinical factors. In the entire donor cohort, we identified 1,825 mtDNA variants, including 67 potential pathogenic variants. Genetic variants on MT-CYB and MT-ND5 genes were identified as independent predictors of posttransplant outcomes. Integration of donor mtDNA variants into the models based on the International Prognostic Scoring System-Revised (IPSS-R) could capture more prognostic information for MDS patients. Sensitivity analysis in 397 unrelated donors obtained similar results. More importantly, we found that incorporating donor mtDNA variants with donor age and the degree of HLA-matching could help to identify "suboptimal" younger HLA-well-matched unrelated donors and "optimal" older HLA-partially/mismatched unrelated donors. Our study shows that mtDNA variants in donors, including those from unrelated donors, hold prognostic value for MDS patients undergoing allo-HCT and augment the prognostic stratification of current scoring systems. These findings present an opportunity to refine donor selection strategies and improve posttransplant outcomes for MDS patients.
    DOI:  https://doi.org/10.1186/s13045-024-01622-w
  10. Stem Cell Res Ther. 2024 Nov 04. 15(1): 394
    The role of mitochondrial transfer in the suppression of CD8+ T cell responses by Mesenchymal stem cells.
    Loic Vaillant, Waseem Akhter, Jean Nakhle, Matthieu Simon, Martin Villalba, Christian Jorgensen, Marie-Luce Vignais, Javier Hernandez.
       BACKGROUND: . CD8+ Cytotoxic T lymphocytes play a key role in the pathogenesis of autoimmune diseases and clinical conditions such as graft versus host disease and graft rejection. Mesenchymal Stromal Cells (MSCs) are multipotent cells with tissue repair and immunomodulatory capabilities. Since they are able to suppress multiple pathogenic immune responses, MSCs have been proposed as a cellular therapy for the treatment of immune-mediated diseases. However, the mechanisms underlying their immunosuppressive properties are not yet fully understood. MSCs have the remarkable ability to sense tissue injury and inflammation and respond by donating their own mitochondria to neighboring cells. Whether mitochondrial transfer has any role in the repression of CD8+ responses is unknown.
    METHODS AND RESULTS: . We have utilized CD8+ T cells from Clone 4 TCR transgenic mice that differentiate into effector cells upon activation in vitro and in vivo to address this question. Allogeneic bone marrow derived MSCs, co-cultured with activated Clone 4 CD8+ T cells, decreased their expansion, the production of the effector cytokine IFNγ and their diabetogenic potential in vivo. Notably, we found that during this interaction leading to suppression, MSCs transferred mitochondria to CD8+ T cells as evidenced by FACS and confocal microscopy. Transfer of MSC mitochondria to Clone 4 CD8+ T cells also resulted in decreased expansion and production of IFNγ upon activation. These effects overlapped and were additive with those of prostaglandin E2 secreted by MSCs. Furthermore, preventing mitochondrial transfer in co-cultures diminished the ability of MSCs to inhibit IFNγ production. Finally, we demonstrated that both MSCs and MSC mitochondria downregulated T-bet and Eomes expression, key transcription factors for CTL differentiation, on activated CD8+ T cells.
    CONCLUSION: . In this report we showed that MSCs are able to interact with CD8+ T cells and transfer them their mitochondria. Mitochondrial transfer contributed to the global suppressive effect of MSCs on CD8+ T cell activation by downregulating T-bet and Eomes expression resulting in impaired IFNγ production of activated CD8+ T cells.
    Keywords:  Autoimmunity; CD8+ T cells; Immunotherapy; Mesenchymal stem/stromal cells; Mitochondrial transfer
    DOI:  https://doi.org/10.1186/s13287-024-03980-1
  11. J Intellect Disabil Res. 2024 Nov 06. e13197
    High frequency of mitochondrial DNA rearrangements in the peripheral blood of adults with intellectual disability.
    B K Bulduk, J Tortajada, L Torres-Egurrola, A Valiente-Pallejà, R Martínez-Leal, E Vilella, H Torrell, G Muntané, L Martorell.
       BACKGROUND: Mitochondrial DNA (mtDNA) rearrangements are recognised factors in mitochondrial disorders and ageing, but their involvement in neurodevelopmental disorders, particularly intellectual disability (ID) and autism spectrum disorder (ASD), remains poorly understood. Previous studies have reported mitochondrial dysfunction in individuals with both ID and ASD. The aim of this study was to investigate the prevalence of large-scale mtDNA rearrangements in ID and ID with comorbid ASD (ID-ASD).
    METHOD: We used mtDNA-targeted next-generation sequencing and the MitoSAlt high-throughput computational pipeline in peripheral blood samples from 76 patients with ID (mean age 52.5 years, 37% female), 59 patients with ID-ASD (mean age 41.3 years, 46% female) and 32 healthy controls (mean age 42.4 years, 47% female) from Catalonia.
    RESULTS: The study revealed a high frequency of mtDNA rearrangements in patients with ID, with 10/76 (13.2%) affected individuals. However, the prevalence was significantly lower in patients with ID-ASD 1/59 (1.7%) and in HC 1/32 (3.1%). Among the mtDNA rearrangements, six were identified as deletions (median size 6937 bp and median heteroplasmy level 2.3%) and six as duplications (median size 10 455 bp and median heteroplasmy level 1.9%). One of the duplications, MT-ATP6 m.8765-8793dup (29 bp), was present in four individuals with ID with a median heteroplasmy level of 3.9%.
    CONCLUSIONS: Our results show that mtDNA rearrangements are frequent in patients with ID, but not in those with ID-ASD, when compared to HC. Additionally, MitoSAlt has demonstrated high sensitivity and accuracy in detecting mtDNA rearrangements, even at very low heteroplasmy levels in blood samples. While the high frequency of mtDNA rearrangements in ID is noteworthy, the role of these rearrangements is currently unclear and needs to be confirmed with further data, particularly in post-mitotic tissues and through age-matched control studies.
    Keywords:  Autism spectrum disorder; Deletion; Duplication; Intellectual disability; MitoSAlt; Mitochondrial DNA
    DOI:  https://doi.org/10.1111/jir.13197
  12. Res Involv Engagem. 2024 Nov 06. 10(1): 117
    Patient and public involvement in the design of an international clinical trial: real world experience.
    Gwenda Simons, Helen Jones, Ian Clarke, Firoza Davies, Stacey Grealis, Elspeth Insch, Hameed Kahn, Joanne Lloyd, Al Richards, Hayley Rose, Ruth Williams, Maarten de Wit, Clarissa Woodcock, Leigh Romaniuk, Michelle Bardgett, Arthur G Pratt, Marie Falahee.
       BACKGROUND: The value of patient and public involvement (PPI) during the earliest stages of clinical trial development, and prior to the award of substantive funding, is widely recognised. However, it is often under-resourced and PPI processes during this phase are rarely reported in detail. Having benefitted from seed funding to develop an international clinical trial proposal, we sought to describe and appraise PPI activities and processes that support pre-award co-development.
    METHODS: A 12-month "accelerator" award facilitated development of a substantive funding application to deliver the Rheumatoid Arthritis Prevention PlatfORm Trial (RAPPORT), conceived to prioritise preventative interventions for people at risk of RA. PPI partners, including individuals at risk of rheumatoid arthritis (RA), RA patients, relatives and members of the public, provided feedback on key trial design issues through online meetings, a feedback form and emails. PPI processes employed during the one-year accelerator project were thereafter evaluated by PPI partners using an anonymous online feedback form with reference to National Institute of Health and Care Research (NIHR) UK standards for public involvement in research.
    RESULTS: Sixteen out of the 25-strong PPI partner panel completed an online feedback form (64%). Respondents perceived PPI processes positively in relation to all NIHR standard domains. Several key facilitators and challenges were identified, including the need for adequate PPI funding during pre-award phases of research, strategies for creating an inclusive environment, flexibility around levels of involvement, and challenges in achieving representatively diverse participation, and the importance of communicating transparent processes for role-assignment and time-reimbursement.
    CONCLUSIONS: In general, RAPPORT was considered an example of PPI well done, and in line with UK standards for public involvement in research. Facilitators and challenges of relevance for the development of future translational and clinical trial funding applications are highlighted.
    Keywords:  Clinical trials; Evaluation; Patient and public involvement and engagement; Pre-award
    DOI:  https://doi.org/10.1186/s40900-024-00642-7
  13. Res Dev Disabil. 2024 Nov 04. pii: S0891-4222(24)00200-2. [Epub ahead of print]155 104868
    Being the other child - A systematic review on the quality of life and mental health of siblings of children with rare diseases.
    Johannes Boettcher, Fabian Kröger, Nele Reinsberg, Silke Wiegand-Grefe, Holger Zapf.
       BACKGROUND: Siblings of children with rare diseases play a crucial yet often overlooked role in the family dynamic and their sibling's illness experience. This systematic review aims to synthesize and evaluate existing research on the Quality of Life (QoL) and mental health outcomes of siblings in this unique context.
    METHODS: We performed a systematic literature search in six databases, including quantitative studies on siblings of children with rare diseases. A total of 37 reports (34 studies) met the inclusion criteria. Siblings' QoL and mental health were compared to normative samples and their siblings with a rare disease. Risk factors for siblings' QoL and mental health were systematically investigated. Moreover, methodological quality and risk of bias were analyzed.
    RESULTS: The findings revealed that siblings of children with rare diseases experience reduced QoL and mental health compared to norm data, although results have been mixed. Psychosocial risk factors like parental family stress factors, compared to disease-specific risk factors, play a particular role in the QoL and mental health of siblings of children with rare diseases.
    CONCLUSION: Healthcare providers should consider and address the potential psychosocial impact on QoL and mental health in siblings of children with rare diseases. Additionally, opportunities to bridge existing research gaps and suggestions for advancing theory-driven research in this area will be discussed.
    Keywords:  Mental health; Quality of Life; Rare diseases; Siblings; Systematic review
    DOI:  https://doi.org/10.1016/j.ridd.2024.104868
  14. Bratisl Lek Listy. 2024 ;125(11): 693-700
    Perspective targeted diagnosis and therapy of mitochondrial bioenergetics across different diagnoses.
    Monika Glevicka, Maria Komlosi, Maria Szantova, Anna Gvozdjakova, Jarmila Kucharska, Zuzana Sumbalova.
      Important metabolic variables that lead to the development of many diseases, including "mitochondrial diseases," include increased oxidative stress and mitochondrial malfunction. Given that the clinical picture and metabolic alterations in individuals suspected of having mitochondrial illnesses lack distinct characteristics, the development of sensitive and specific diagnostic techniques to detect alterations in mitochondrial bioenergetics is imperative. High-resolution respirometry (HRR), is a minimally invasive technique that enables the analysis of mitochondrial function in platelets taken from peripheral blood. This method allows for the detection of even the most subtle changes prior to disease development. HRR can identify minute variations in mitochondrial bioenergetics. Determining mitochondrial function and endogenous levels of CoQ10 in platelets can aid in the early detection of pathobiochemical changes in mitochondria and assessment of treatment efficacy. When combined with the measurement of endogenous coenzyme Q10 levels, HRR may be an effective approach for early identification of compromised mitochondrial function along with monitoring the therapeutic outcomes. Supplementing with coenzyme Q10, applying molecular hydrogen, transplanting mitochondria, and applying platelet-rich plasma (PRP) are some of the therapeutic strategies utilized to enhance mitochondrial function and reduce oxidative stress (Tab. 1, Fig. 1, Ref. 62). Text in PDF www.elis.sk Keywords: mitochondrial dysfunction, oxidative stress, mitochondrial bioenergetics, high-resolution respirometry, therapeutic approaches.
    DOI:  https://doi.org/10.4149/BLL_2024_105
  15. Curr Biol. 2024 Nov 04. pii: S0960-9822(24)01346-0. [Epub ahead of print]34(21): R1067-R1068
    Mitochondrial nucleoids.
    Eve V Kakudji, Samantha C Lewis.
      Eve Kakudji and Samantha Lewis discuss the structure and function of mitochondrial nucleoids - large nucleoprotein complexes containing mitochondrial DNA and the regulatory factors necessary for its packaging, replication, transcription, and repair.
    DOI:  https://doi.org/10.1016/j.cub.2024.09.078
  16. Curr Med Res Opin. 2024 Nov 09. 1-2
    You don't have celiac disease: a patient perspective on potential issues with stress leading to misdiagnosis.
    Ashley M Snyder.
      
    DOI:  https://doi.org/10.1080/03007995.2024.2425063
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