1. Therapy Prospects for Mitochondrial DNA Maintenance Disorders
- Author
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Yolanda Cámara, Ferran Vila-Julià, David Molina-Granada, Maria Jesús Melià, Javier Torres-Torronteras, Miguel Molina-Berenguer, Ramon Martí, Elena García-Arumí, Javier Ramón, Institut Català de la Salut, [Ramón J, Vila-Julià F, Molina-Granada D, Molina-Berenguer M, Melià MJ, García-Arumí E, Torres-Torronteras J, Cámara Y, Martí R] Grup de Recerca en Malalties Neuromusculars i Mitocondrials, Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
0301 basic medicine ,Mitochondrial Diseases ,Genetic enhancement ,medicine.medical_treatment ,Genetic Phenomena::DNA Replication [PHENOMENA AND PROCESSES] ,Multiple deletions ,Review ,Nutritional and Metabolic Diseases::Metabolic Diseases::Mitochondrial Diseases [DISEASES] ,Mitochondrion ,Liver transplantation ,Bioinformatics ,0302 clinical medicine ,Nucleoside ,Biology (General) ,Otros calificadores::/terapia [Otros calificadores] ,Spectroscopy ,depletion ,mtDNA ,Disease Management ,General Medicine ,multiple deletions ,Combined Modality Therapy ,gene therapy ,Computer Science Applications ,Mitochondria ,mitochondria ,Chemistry ,Mitocondris - Malalties - Tractament ,Disease Susceptibility ,Stem cell ,enfermedades nutricionales y metabólicas::enfermedades metabólicas::enfermedades mitocondriales [ENFERMEDADES] ,DNA Replication ,Mitochondrial DNA ,replication ,ADN - Duplicació ,QH301-705.5 ,Replication ,Dysfunctional family ,nucleoside ,DNA, Mitochondrial ,Catalysis ,Mitochondrial Proteins ,Inorganic Chemistry ,03 medical and health sciences ,Depletion ,fenómenos genéticos::replicación del ADN [FENÓMENOS Y PROCESOS] ,Gene therapy ,medicine ,Animals ,Humans ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,therapy ,business.industry ,Organic Chemistry ,Other subheadings::/therapy [Other subheadings] ,Mtdn ,Transplantation ,Clinical trial ,030104 developmental biology ,Gene Expression Regulation ,Mutation ,Therapy ,business ,030217 neurology & neurosurgery - Abstract
Esgotament; Teràpia gènica; Mitocondris Mitochondria; Depletion; Gene therapy Agotamiento; Terapia génica; Mitocondrias Mitochondrial DNA depletion and multiple deletions syndromes (MDDS) constitute a group of mitochondrial diseases defined by dysfunctional mitochondrial DNA (mtDNA) replication and maintenance. As is the case for many other mitochondrial diseases, the options for the treatment of these disorders are rather limited today. Some aggressive treatments such as liver transplantation or allogeneic stem cell transplantation are among the few available options for patients with some forms of MDDS. However, in recent years, significant advances in our knowledge of the biochemical pathomechanisms accounting for dysfunctional mtDNA replication have been achieved, which has opened new prospects for the treatment of these often fatal diseases. Current strategies under investigation to treat MDDS range from small molecule substrate enhancement approaches to more complex treatments, such as lentiviral or adenoassociated vector-mediated gene therapy. Some of these experimental therapies have already reached the clinical phase with very promising results, however, they are hampered by the fact that these are all rare disorders and so the patient recruitment potential for clinical trials is very limited.
- Published
- 2021