Personalized Medicine in Mitochondrial Health and Disease: Molecular Basis of Therapeutic Approaches Based on Nutritional Supplements and Their Analogs.
Vincenzo Tragni, Guido Primiano, Albina Tummolo, Lucas Cafferati Beltrame, Gianluigi La Piana, Maria Noemi Sgobba, Maria Maddalena Cavalluzzi, Giulia Paterno, Ruggiero Gorgoglione, Mariateresa Volpicella, Lorenzo Guerra, Domenico Marzulli, Serenella Servidei, Anna De Grassi, Giuseppe Petrosillo, Giovanni Lentini, Ciro Leonardo Pierri
Author Information
Vincenzo Tragni: Department of Biosciences, Biotechnologies, Biopharmaceutics, University of Bari Aldo Moro, Via E. Orabona, 4, 70125 Bari, Italy. ORCID
Albina Tummolo: Department of Metabolic Diseases, Clinical Genetics and Diabetology, Giovanni XXIII Children Hospital, Azienda Ospedaliero-Universitaria Consorziale, Via Amendola 207, 70126 Bari, Italy.
Lucas Cafferati Beltrame: Department of Biosciences, Biotechnologies, Biopharmaceutics, University of Bari Aldo Moro, Via E. Orabona, 4, 70125 Bari, Italy.
Gianluigi La Piana: Department of Biosciences, Biotechnologies, Biopharmaceutics, University of Bari Aldo Moro, Via E. Orabona, 4, 70125 Bari, Italy. ORCID
Maria Noemi Sgobba: Department of Biosciences, Biotechnologies, Biopharmaceutics, University of Bari Aldo Moro, Via E. Orabona, 4, 70125 Bari, Italy.
Maria Maddalena Cavalluzzi: Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy. ORCID
Giulia Paterno: Department of Metabolic Diseases, Clinical Genetics and Diabetology, Giovanni XXIII Children Hospital, Azienda Ospedaliero-Universitaria Consorziale, Via Amendola 207, 70126 Bari, Italy.
Ruggiero Gorgoglione: Department of Biosciences, Biotechnologies, Biopharmaceutics, University of Bari Aldo Moro, Via E. Orabona, 4, 70125 Bari, Italy.
Mariateresa Volpicella: Department of Biosciences, Biotechnologies, Biopharmaceutics, University of Bari Aldo Moro, Via E. Orabona, 4, 70125 Bari, Italy. ORCID
Lorenzo Guerra: Department of Biosciences, Biotechnologies, Biopharmaceutics, University of Bari Aldo Moro, Via E. Orabona, 4, 70125 Bari, Italy.
Domenico Marzulli: Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), National Research Council (CNR), 70126 Bari, Italy.
Anna De Grassi: Department of Biosciences, Biotechnologies, Biopharmaceutics, University of Bari Aldo Moro, Via E. Orabona, 4, 70125 Bari, Italy. ORCID
Giuseppe Petrosillo: Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), National Research Council (CNR), 70126 Bari, Italy. ORCID
Giovanni Lentini: Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy. ORCID
Ciro Leonardo Pierri: Department of Biosciences, Biotechnologies, Biopharmaceutics, University of Bari Aldo Moro, Via E. Orabona, 4, 70125 Bari, Italy. ORCID
Mitochondrial diseases (MDs) may result from mutations affecting nuclear or mitochondrial genes, encoding mitochondrial proteins, or non-protein-coding mitochondrial RNA. Despite the great variability of affected genes, in the most severe cases, a neuromuscular and neurodegenerative phenotype is observed, and no specific therapy exists for a complete recovery from the disease. The most used treatments are symptomatic and based on the administration of antioxidant cocktails combined with antiepileptic/antipsychotic drugs and supportive therapy for multiorgan involvement. Nevertheless, the real utility of antioxidant cocktail treatments for patients affected by MDs still needs to be scientifically demonstrated. Unfortunately, clinical trials for antioxidant therapies using α-tocopherol, ascorbate, glutathione, riboflavin, niacin, acetyl-carnitine and coenzyme Q have met a limited success. Indeed, it would be expected that the employed antioxidants can only be effective if they are able to target the specific mechanism, i.e., involving the central and peripheral nervous system, responsible for the clinical manifestations of the disease. Noteworthily, very often the phenotypes characterizing MD patients are associated with mutations in proteins whose function does not depend on specific cofactors. Conversely, the administration of the antioxidant cocktails might determine the suppression of endogenous oxidants resulting in deleterious effects on cell viability and/or toxicity for patients. In order to avoid toxicity effects and before administering the antioxidant therapy, it might be useful to ascertain the blood serum levels of antioxidants and cofactors to be administered in MD patients. It would be also worthwhile to check the localization of mutations affecting proteins whose function should depend (less or more directly) on the cofactors to be administered, for estimating the real need and predicting the success of the proposed cofactor/antioxidant-based therapy.
