bims-polgdi 2025-08-03 papers

Issue of 2025–08–03
five papers selected by
Luca Bolliger, lxBio

Adv Exp Med Biol. 2025 ;1467 173-175

Mitochondrial Disorder: Kearns-Sayre Syndrome.

Benjamin Kuang-Chien Chiang, Stephen H Tsang, Alicia R P Aycinena, Tarun Sharma.

Mitochondrial DNA (mtDNA) deletions can be identified, and rarely point mutation.

Keywords: KSS; Kearns-Sayre syndrome; Mitochondrial disorder

DOI: https://doi.org/10.1007/978-3-031-72230-1_30

J Inherit Metab Dis. 2025 Jul;48(4): e70065

Therapies for Mitochondrial Disease: Past, Present, and Future.

Megan Ball, Nicole J van Bergen, Alison G Compton, David R Thorburn, Shamima Rahman, John Christodoulou.

Mitochondrial disease is a diverse group of clinically and genetically complex disorders caused by pathogenic variants in nuclear or mitochondrial DNA-encoded genes that disrupt mitochondrial energy production or other important mitochondrial pathways. Mitochondrial disease can present with a wide spectrum of clinical features and can often be difficult to recognize. These conditions can be devastating; however, for the majority, there is no targeted treatment. In the last 60 years, mitochondrial medicine has experienced significant evolution, moving from the pre-molecular era to the Age of Genomics in which considerable gene discovery and advancement in our understanding of the pathophysiology of mitochondrial disease have been made. In the last decade, in response to the urgent need for effective treatments, a wide range of emerging therapies have been developed, driven by innovative approaches addressing both the genetic and cellular mechanisms underpinning the diseases. Emerging therapies include dietary intervention, small molecule therapies aimed to restore mitochondrial function, stem cell or liver transplantation, and gene or RNA-based therapies. However, despite these advances, translation to clinical practice is complicated by the sheer genetic and clinical complexity of mitochondrial disease, difficulty in efficient and precise delivery of therapies to affected tissues, rarity of individual genetic conditions, lack of reliable biomarkers and clinically relevant outcome measures, and the dearth of natural history data. This review examines the latest developments in the pursuit to identify effective treatments for mitochondrial disease and discusses the barriers impeding their success in translation to clinical practice. While treatment for mitochondrial disease may be on the horizon, many challenges must be addressed before it can become a reality.

Keywords: clinical trials; gene therapy; mitochondrial disease; small molecule therapy; treatment

DOI: https://doi.org/10.1002/jimd.70065

Int J Mol Sci. 2025 Jul 11. pii: 6645. [Epub ahead of print]26(14):

Causes of and Solutions to Mitochondrial Disorders: A Literature Review.

Vera Belousova, Irina Ignatko, Irina Bogomazova, Elena Sosnova, Svetlana Pesegova, Anastasia Samusevich, Evdokiya Zarova, Madina Kardanova, Oxana Skorobogatova, Anna Maltseva.

Mitochondria are currently of great interest to scientists. The role of mitochondrial DNA (mtDNA) mutations has been proven in the genesis of more than 200 pathologies, which are called mitochondrial disorders. Therefore, the study of mitochondria and mitochondrial DNA is of great interest not only for understanding cell biology but also for the treatment and prevention of many mitochondria-related pathologies. There are two main trends of mitochondrial therapy: mitochondrial replacement therapy (MRT) and mitochondrial transplantation therapy (MTT). Also, there are two main categories of MRT based on the source of mitochondria. The heterologous approach includes the following methods: pronuclear transfer technique (PNT), maternal spindle transfer (MST), Polar body genome transfer (PBT) and germinal vesicle transfer (GVT). An alternative approach is the autologous method. One promising autologous technique was the autologous germline mitochondrial energy transfer (AUGMENT), which involved isolating oogonial precursor cells from the patient, extracting their mitochondria, and then injecting them during ICSI. Transmission of defective mtDNA to the next generation can also be prevented by using these approaches. The development of a healthy child, free from genetic disorders, and the prevention of the occurrence of lethal mitochondrial disorders are the main tasks of this method. However, a number of moral, social, and cultural objections have restricted its exploration, since humanity first encountered the appearance of a three-parent baby. Therefore, this review summarizes the causes of mitochondrial diseases, the various methods involved in MRT and the results of their application. In addition, a new technology, mitochondrial transplantation therapy (MTT), is currently being actively studied. MTT is an innovative approach that involves the introduction of healthy mitochondria into damaged tissues, leading to the replacement of defective mitochondria and the restoration of their function. This technology is being actively studied in animals, but there are also reports of its use in humans. A bibliographic review in PubMed and Web of Science databases and a search for relevant clinical trials and news articles were performed. A total of 81 publications were selected for analysis. Methods of MRT procedures were reviewed, their risks described, and the results of their use presented. Results of animal studies of the MTT procedure and attempts to apply this therapy in humans were reviewed. MRT is an effective way to minimize the risk of transmission of mtDNA-related diseases, but it does not eliminate it completely. There is a need for global legal regulation of MRT. MTT is a new and promising method of treating damaged tissues by injecting the body's own mitochondria. The considered methods are extremely good in theory, but their clinical application in humans and the success of such therapy remain a question for further study.

Keywords: mitochondrial DNA; mitochondrial disorders; mitochondrial replacement therapy; mitochondrial transplantation therapy; review; three-parent baby

DOI: https://doi.org/10.3390/ijms26146645

Nat Med. 2025 Jul 30.

Three-donor IVF prevents mitochondrial disease.

Karen O'Leary.

Keywords: Genetics; Reproductive techniques ; Technology

DOI: https://doi.org/10.1038/d41591-025-00047-3