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The scientific team of Sánchez Alcázar advances in the treatment of mitochondrial diseases

A CABD study led by UPO professor José Antonio Sánchez Alcázar demonstrates how pathological alterations in the mitochondrial mutation LIPT1 can be corrected by activators of UPRmt, a mitochondrial protection mechanism.


Mitochondrial diseases, a group of genetic disorders that affect cellular energy production, remain one of the greatest challenges in modern medicine. With a prevalence of more than 1 in 5000 people, these diseases often lack effective treatments. However, a research team at the CABD in Seville, led by Professor José Antonio Sánchez Alcázar, has made significant advances in the development of new therapeutic strategies to combat these pathologies.

The recently published study addresses the treatment of the mitochondrial LIPT1 mutation by activating the mitochondrial response to misfolded proteins (UPRmt). The LIPT1 mutation causes respiratory chain deficiencies and very severe clinical pictures such as Leigh Syndrome or subacute necrotizing encephalomyelopathy, a progressive neurodegenerative disease, often fatal in early life.



Summary of the results

Using fibroblasts from an affected patient, the team discovered that a pharmacological cocktail composed of antioxidants and mitochondrial enhancers can correct the pathological alterations caused by this mutation. This therapy not only enabled cell survival under adverse conditions, but also restored critical functions such as mitochondrial protein lipoylation and cellular bioenergetics.

This advance is part of the MITOCURE platform, a personalized precision medicine project developed by Dr. Sánchez Alcázar's team, which evaluates the effectiveness of treatments in cells derived from patients with different mitochondrial mutations. MITOCURE is currently applying this methodology to more than 30 different mutations that directly or indirectly affect energy formation by mitochondria, opening new hopes for the treatment of these complex diseases.

“Activation of cellular compensatory mechanisms, such as UPRmt, is a promising therapeutic strategy for mitochondrial diseases,” say the researchers. The mutations studied by this research group affect both genes located in nuclear DNA (COQ7, GFM1, COX15, NDUFAF6, NDUFS1 and NDUFS4) and in mitochondrial DNA (ND3).

The collaboration with the Virgen Macarena University Hospital in Seville to take these findings to clinical trials underscores the importance of this advance for precision medicine. Thus, with the aim of transferring the results of the research to patients, Dr. Sánchez Alcázar's group collaborates closely with the team of Dr. Andrés Rodríguez Sacristán of the Neuropediatrics Unit of the Pediatrics Service of the Virgen Macarena University Hospital.

This discovery could thus mark a turning point in the way mitochondrial diseases are approached, offering new therapeutic avenues to patients who until now only had palliative treatments.

This research group at the Pablo de Olavide University, which carries out its work at the Andalusian Center for Developmental Biology (a joint center of the CSIC, UPO and the Andalusian Regional Government), applies this working method based on personalized precision medicine, in addition to the MITOCURE project, in its different projects, such as MYOCURE (focused on congenital myopathies), BRAINCURE (focused on neurodegeneration due to iron accumulation and demyelinating diseases), and CANCERCURE (focused on the search for personalized treatments for genetic susceptibility to cancer).

The referred scientific article:

David Gómez-Fernández, Ana Romero-González, Juan M. Suárez-Rivero, Paula Cilleros-Holgado, Mónica Álvarez-Córdoba, Rocío Piñero-Pérez, José Manuel Romero-Domínguez, Diana Reche-López, Alejandra López-Cabrera, Salvador Ibáñez-Mico, Marta Castro de Oliveira, Andrés Rodríguez-Sacristán, Susana González-Granero, José Manuel García-Verdugo, and José A. Sánchez-Alcázar. A multi-target pharmacological correction of a lipoyltransferase LIPT1 gene mutation in patient-derived cellular models. Antioxidants (Basel). 2024 Aug 22;13(8):1023. doi: 10.3390/antiox13081023.

This press release was written in collaboration with the Communication team from UPO