bims-curels 2025-08-24 papers

bims-curels

Biomed News

on Leigh syndrome

Issue of 2025–08–24
six papers selected by
Cure Mito Foundation

Significance of Mitochondrial Dynamics in Reproductive Physiology: Current and Emerging Horizons in Mitochondrial Therapy for Assisted Reproductive Technologies.
Diagnosing Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS) Syndrome in a Young Adult Female Patient With Seizures and Lactic Acidosis.
Parental Experiences of Receiving a Rare Genetic Disease Diagnosis for Their Child on Diagnosis Day.
NF-κB signalling pathway in neurodegenerative diseases: Acupuncture as a potential therapeutic approach.
Exploring the experience of communication in healthcare settings with parents of children with a rare genetic condition: "It's the more negative ones that you remember".
Putting control into parents' hands: Parent experiences with a genomic results e-booklet.

Reprod Med Biol. 2025 Jan-Dec;24(1):24(1): e12672

Significance of Mitochondrial Dynamics in Reproductive Physiology: Current and Emerging Horizons in Mitochondrial Therapy for Assisted Reproductive Technologies.

Sanath Udayanga Kankanam Gamage, Yoshiharu Morimoto.

   Background: Mitochondria play a critical role in cellular bioenergetics and signaling, with particular importance in the context of reproductive biology. This review summarizes their role in reproduction and explores current and emerging mitochondrial therapies for fertility treatment.
Methods: A comprehensive literature search using terms like mitochondria, infertility, reproduction, gametes, mitochondrial replacement, and mitochondrial transplantation identified relevant studies on mitochondria's role in gametogenesis, fertilization, and early embryonic development in relevant databases. Selected publications were reviewed and summarized to present current and future mitochondrial therapies for fertility.
Main Findings: Mitochondrial dynamics and functions are critical for meeting the energy requirements of essential reproductive processes, including gametogenesis, fertilization, and early embryonic development. Dysregulation of mitochondrial function has been associated with a range of reproductive disorders, such as infertility, recurrent pregnancy loss, and maternally inherited mitochondrial diseases. Emerging therapeutic strategies, such as mitochondrial replacement therapy, antioxidant supplementation, and mitochondrial transplantation, offer promising avenues for overcoming these challenges and improving reproductive outcomes.
Conclusions: Utilizing mitochondrial-based therapies represents a promising and innovative approach in the advancement of fertility treatments. Ongoing research and clinical development in this area hold significant potential to enhance reproductive outcomes and improve the quality of life for individuals and couples facing fertility challenges.

Keywords:  ascent; infertility; mitochondria; mitochondrial dysfunction; mitochondrial therapies for infertility; mitochondrial transplantation; reproductive aging

DOI:  https://doi.org/10.1002/rmb2.12672
Cureus. 2025 Jul;17(7): e88031

Diagnosing Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS) Syndrome in a Young Adult Female Patient With Seizures and Lactic Acidosis.

Ishan A Sane, Jessica R Gupte.

  The aim of this case report is to highlight the diagnostic challenges and clinical presentation of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, which is a rare, maternally inherited mitochondrial disorder. MELAS typically manifests with a constellation of neurological and systemic symptoms, including seizures, lactic acidosis, stroke-like episodes, and progressive cognitive decline. Mutations in mitochondrial DNA impair oxidative phosphorylation and result in widespread cellular dysfunction. We report the case of a 33-year-old female patient who presented with seizures, altered mental status, and focal neurological deficits. Laboratory evaluation revealed elevated serum lactate, and neuroimaging demonstrated stroke-like lesions not confined to vascular territories. A muscle biopsy showed abnormal mitochondrial accumulation, and electron microscopy detected ragged red fibers, which is confirmatory of mitochondrial cytopathy. The patient was managed symptomatically in the intensive care unit with antiepileptics, corticosteroids, and a mitochondrial cocktail comprising coenzyme Q10, L-arginine, L-carnitine, and B-complex vitamins. Plasmapheresis was also performed during initial management due to diagnostic uncertainty. The patient showed gradual clinical improvement and was discharged on supportive therapy. This case emphasizes the importance of early recognition of atypical stroke-like presentations and metabolic derangements in young patients. MELAS syndrome should be considered in the differential diagnosis of stroke mimics, especially in the absence of vascular risk factors. Timely diagnosis, supportive care, and long-term follow-up, including genetic counselling, are essential for optimizing outcomes in these patients.

Keywords:  encephalomyopathy; lactic acidosis; melas syndrome; mitochondrial disorder; red ragged fibers; stroke-like episodes

DOI:  https://doi.org/10.7759/cureus.88031
Am J Med Genet A. 2025 Aug 17. e64223

Parental Experiences of Receiving a Rare Genetic Disease Diagnosis for Their Child on Diagnosis Day.

Isabel Bullock, Kristen Fishler Malone, Abigail Turnwald.

  Literature exploring the experiences of parents of children with rare genetic conditions on "Diagnosis Day," the day a diagnosis is given, is limited. We created a survey to further explore these experiences. Parents of children with rare genetic conditions 18 years or younger were recruited through rare disease organizations and social media. Seven hundred and seventeen participants, representing 229 rare diseases, met the inclusion criteria. Most parents received their child's diagnosis in person. Other parents received the diagnosis by phone or telehealth. Most parents (73%) were satisfied with where the diagnosis was given. Parents experienced a range of emotions on Diagnosis Day, most commonly hopelessness, sadness, confusion, and relief. With a longer time to diagnosis, participants reported more positive emotions and fewer negative emotions (p < 0.001). The information parents considered most important on Diagnosis Day included details about quality of life, medical management, inheritance, and connecting with other families. Nearly half of parents felt that providers could have done something different when delivering the diagnosis, including providing specific information on the diagnosis, asking parents to decide where results are given, asking about including other family members, and providing compassion and empathy. Together, these findings can be used to improve the Diagnosis Day experience for parents.

Keywords:  diagnosis day; genetic diagnosis; genetic testing; rare disease; result disclosure

DOI:  https://doi.org/10.1002/ajmg.a.64223
Brain Res. 2025 Aug 17. pii: S0006-8993(25)00456-1. [Epub ahead of print] 149893

NF-κB signalling pathway in neurodegenerative diseases: Acupuncture as a potential therapeutic approach.

Yangyang Wang, Yuanfang Zhou, Hao Tian, Qifu Li, Yan Chen, Lu Wang, Zihan Yin, Jun Zhou, Fanrong Liang.

  The NF-κB signaling pathway plays a crucial role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, particularly through its role in the regulation neuroinflammation, oxidative stress, protein misfolding, and apoptosis. Emerging evidence suggests that acupuncture modulates the NF-κB pathway, thus offering therapeutic potential by mitigating neuroinflammation, reducing oxidative stress, and protecting mitochondrial function. Specifically, acupuncture inhibits NF-κB activation, downregulates pro-inflammatory mediators like TNF-α and IL-6, and mitigates neurotoxicity and apoptosis. These effects are substantiated in animal models of Alzheimer's and Parkinson's diseases, with preliminary evidence in amyotrophic lateral sclerosis models. However, current studies largely rely on preclinical models with limited acupoint selection, short observation periods, and a lack of standardized protocols, posing challenges for translation to clinical settings. Future research should prioritize well-designed clinical trials, expand acupoint combinations, and explore synergistic effects with conventional therapies, aiming to maximize acupuncture's therapeutic efficacy in neurodegenerative diseases.

Keywords:  Acupuncture; Alzheimer’s disease; NF-κB; Neurodegenerative diseases; Parkinson’s disease

DOI:  https://doi.org/10.1016/j.brainres.2025.149893
J Genet Couns. 2025 Aug;34(4): e70102

Exploring the experience of communication in healthcare settings with parents of children with a rare genetic condition: "It's the more negative ones that you remember".

Lucy Burbury, Samantha Ayres, Jackie Boyle, Heather Renton, Aideen McInerney-Leo.

  Rare genetic conditions (molecularly diagnosed and undiagnosed) of childhood are typically complex in presentation and natural history. Consequently, the diagnostic odyssey can result in families having multiple interactions with diverse healthcare professionals. The quality of these interactions has been relatively underexplored. Semi-structured interviews explored various parental experiences of communications with genetics and non-genetics healthcare professionals in Australia. Fourteen parents (12 mothers and 2 fathers) of children with rare conditions (12 diagnosed and 2 undiagnosed) agreed to participate. Each interview was recorded, transcribed, and explored using reflexive thematic analysis. Six themes pertaining to the parental experience of communication around genomics were generated. The first is "the need for family-centered care" where parents described the importance of involving their child in discussions, even when they are non-verbal. Second, "the value of à la carte communication", highlighted that respectful communication, tailored the needs of each family, was highly valued and improved understanding. The third and fourth themes were "technical language is overwhelming" and "negative word choices can be 'soul destroying'," respectively. These themes captured how insensitive and/or overly complex discussions, can have negative and lasting effects. The fifth theme, "all results (diagnostic and non-diagnostic) are significant," underscored the profound emotional impact of receiving genetic results. The final theme, "where to from here?" revealed that many parents felt abandoned after receiving genetic results and were left to "sink or swim." Only half of participants had seen a genetic counselor and none could recall being referred to support groups. In conclusion, this study emphasizes the power of language, empathy, and clear, respectful communication for families affected by rare conditions. Additionally, it highlights that these families should have access to genetic counseling and receive referrals for practical and emotional support regardless of whether their child has a molecular diagnosis.

Keywords:  communication; diagnosed and undiagnosed rare genetic conditions; genetic healthcare professionals; non‐genetic healthcare professionals; parents

DOI:  https://doi.org/10.1002/jgc4.70102
J Genet Couns. 2025 Aug;34(4): e70095

Putting control into parents' hands: Parent experiences with a genomic results e-booklet.

GenCOUNSEL

  We evaluated the clinical use of a customizable, multi-language, Genomic Results Booklet (GRB)-a printable e-booklet co-designed with parents-to provide information and guidance to families post-genomic testing. The GRB provides individual genomic results, with implications and resources, all in family-friendly language. Participants were parents of children offered genomic testing in a pediatric neurology clinic. Two and eight weeks after GRB receipt, parents completed surveys to assess usage of the e-booklet. Parents then had a semi-structured telephone interview about their experiences, which were analyzed using interpretive description. Thirty-four parents received a customized GRB, including versions in Punjabi and Arabic. Seventeen booklets were for pathogenic test results, and the other 17 were for noninformative results. The surveys showed that all families would recommend the GRB and had used its resources or supports. About 80% shared it with others, and 67% described it as helpful in future planning. Analysis of 20 parent-interviews revealed that parents valued understandable, relevant information; a written e-pamphlet; a list of appropriate resources; and practical guidance. The GRB is valued by parents to explain their individual genomic testing results, to provide useful supports, specific resources, and a sense of direction in the weeks after receiving results.

Keywords:  e‐booklet; genetic counseling; genomic results; genomic sequencing; patient resources

DOI:  https://doi.org/10.1002/jgc4.70095