Pulmonary hypertension (high blood pressure that affects arteries in the lungs) is a fatal disease that affects approximately 75 million people globally. Mitochondrial transplantation has been touted as a possible treatment option, but the jury is still out on whether it will be effective enough to cure the illness or to reduce mortality rates.
This is according to Dr Gerald Maarman from the Centre for Cardio‐Metabolic Research in Africa (CARMA) in the Faculty of Medicine and Health Sciences at Stellenbosch University. He conducted a review of current literature on autologous mitochondrial transplantation in the context of other diseases and highlighted its therapeutic potential in pulmonary hypertension, while also addressing several concerns.
Mitochondrial transplantation is a technique to extract mitochondria from a patient's skeletal muscle and transplant it into a damaged organ of the same individual.
The findings of Maarman's review were published in the American Journal of Physiology-Lung Cellular and Molecular Physiology recently.
According to Maarman, pulmonary hypertension is associated with genetic mutations, hypoxia (low levels of oxygen in the lung), structural lung damage, tuberculosis, viral infections (HIV, SARS‐CoV‐2) and the increased production of oxidative stress.
He says because most diseases are caused, in part, by mitochondrial dysfunction (when mitochondria don't produce enough energy for the cells or fail to adapt sufficiently to diseases), mitochondrial transplantation could be a potential therapeutic approach.
“Mitochondrial transplantation is a fairly novel strategy to repair mitochondrial damage and dysfunction in pulmonary hypertension. This type of therapy has been proposed to remedy mitochondrial dysfunction in Parkinson's disease and other neurodegenerative diseases, heart failure, and heart attacks.
“Currently, a few ongoing clinical trials are investigating the usefulness and impact of mitochondrial transplantation in stroke and cardiac ischemia. Therefore, both clinical and experimental models are being used to test mitochondrial transplantation, and imminent findings will provide a better view of its true efficacy."
However, the role of mitochondrial transplantation in pulmonary hypertension remains poorly described, with less than a handful of publications on the topic, adds Maarman.
“With personalised medicine, the thinking is that transplanting a patient's mitochondria from one organ to another may promote overall health. Unfortunately, we still have a long way to go, and mitochondrial transplantation is currently not considered as a form of personalised medicine, but as an experimental therapy under scrutiny."
Maarman highlights a few challenges related to mitochondrial transplantation: the source of exogenous mitochondria may not contain sufficient mitochondria; the process of isolating mitochondria from the muscles could induce ischemic and stress damage to the mitochondria that are designated for transplantation, and this damage could be transferred to the transplant site of the patient; and the mitochondrial uptake and survival in the transplanted region could be disturbed by circulatory factors in the patient's body.
He emphasises that these challenges are surmountable and should not deter researchers from further investigating the effectiveness of mitochondrial transplantation and trying to overcome the challenges in creative ways.
“We must understand that more research is needed before mitochondrial transplantation can be considered an effective therapy, as many of the mechanisms or potential long‐term risks are still unknown.
“Regardless, further studies are warranted and investigating mitochondrial transplantation as a form of treatment could be beneficial to the field of pulmonary hypertension research and healthcare."
- Source: Maarman, G 2022. Reviewing the suitability of mitochondrial transplantation as therapeutic approach for pulmonary hypertension in the era of personalised medicine. American Journal of Physiology-Lung Cellular and Molecular Physiology. doi: org/10.1152/ajplung.00484.2021
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