An important step towards the treatment of mitochondrial diseases

Researchers from the Oregon Health and Science University, working under the leadership of Dr. Shoukhrat Mitalipov and Dr. Hong Ma, have taken the first critical step towards developing new approaches to gene and cell therapy of mitochondrial diseases.

The authors successfully used the mitochondrial replacement method to create healthy embryonic stem cells from the patient's skin cells that initially had mitochondrial DNA mutations. Such mutations can cause a wide range of fatal or severely disabling pathologies, including diabetes mellitus, deafness, diseases of the eyes, digestive tract, heart, as well as dementia and a number of other neurological diseases. To date, there is no effective treatment for such diseases.

In May 2013, Mitalipov demonstrated for the first time the possibility of using the somatic cell nuclei transfer method to create embryonic stem cells from human skin cells. This breakthrough was followed by a six-year period full of achievements. Among them was the application of the nuclear transfer method to create embryonic primate stem cells, as well as the development of an approach that can help prevent the transmission of hereditary mitochondrial diseases to the next generations.

As part of their latest study, scientists isolated skin cells from patients (children and several middle-aged men) with mutations of mitochondrial DNA. The nuclei were removed from the resulting cells, which were subsequently injected into the cytoplasm of eggs obtained from healthy donors. The cytoplasm is a watery substance surrounding the nucleus, which, in addition to other organelles, contains mitochondria, whose function is to supply the cell with energy. Thus, the authors managed to create embryonic stem cells with healthy mitochondria.

The researchers hope that in the future, the technology they have developed can be used to replace diseased tissue by isolating one cell, correcting mutation, multiplying the resulting stem cells and injecting them to the patient to replace non-functional tissue. The nuclear transfer technique provides much more accurate results than classical gene therapy. Instead of embedding synthetic genes into the patient's DNA using a viral vector, it involves the use of mitochondrial genes from a healthy donor.

The authors note that in their work they managed to combine two complementary strategies of cell reprogramming – the creation of induced pluripotent stem cells and the transfer of somatic cell nuclei – to get rid of mutant mitochondrial DNA. This is an important step towards the emergence of effective therapeutic methods for the treatment of patients with mitochondrial diseases.

Article by Hong Ma et al. Metabolic rescue in pluripotent cells from patients with mtDNA disease is published in the journal Nature.

Evgeniya Ryabtseva

Portal "Eternal youth" http://vechnayamolodost.ru based on materials from Oregon Health & Science University:
OHSU scientists unlock first critical step toward gene therapy treatment for patients with mitochondrial disease.