Abstract: Mitochondria are the "energy factory" of cells. Abnormal mitochondrial function can cause more than 300 rare genetic diseases, such as Leigh syndrome (a serious neurological disease that may occur early in infancy) and MELAS (which can lead to muscle weakness, diabetes and Stroke, usually before the age of 40). However, in Parkinson's and other more common diseases, and even in the aging process itself, mitochondrial function gradually declines. Researchers at Massachusetts General Hospital (MGH) have developed a new method to alleviate problems caused by mitochondrial dysfunction, the findings were published in the January 13 issue of the journal Nature Biotechnology.
All cells have mitochondria, which absorb electrons from the food we eat and transfer them to oxygen. If you compare this process to a river running down a mountain, mitochondria are like "waterwheels" that use water to generate energy. However, mitochondrial disease is like a "dam". By blocking this smooth flow, electrons are accumulated, known as redox imbalance, which stops important chemical reactions in the cell. Scientists believe that the toxicity comes from the "waterwheel" is no longer rotating, and the excess electrons eventually overflow into the blood circulation in the form of lactic acid, which can be used as a marker of intracellular diseases.
This new therapy directly targets circulating lactic acid, which can safely dissipate excess electrons and restore redox balance and intracellular flow. Conceptually, the innovation is that this enzyme does not have to enter the cell, it works on the chemicals coming in and going out, which is beneficial to the internal operation of the cell.
Researchers point out that much work remains to be done before LOXCAT is ready for human testing. However, as there are currently few methods to deal with the consequences of mitochondrial dysfunction, this study lays the foundation for a class of injection therapy enzymes that alleviate intracellular redox imbalances by directly targeting circulating redox coupled metabolites, which may have profound influences.
Reference: Patgiri, A., Skinner, O.S., Miyazaki, Y. et al. An engineered enzyme that targets circulating lactate to alleviate intracellular NADH:NAD+ imbalance. Nat Biotechnol (2020) doi:10.1038/s41587-019-0377-7
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Souce: NovoPro 2020-01-18