Compounds similar to the chemical methylene blue, which has been shown to have therapeutic benefits in several diseases, were seen to increase frataxin levels and the production of mitochondria in Friedreich’s ataxia (FA) cells.
The study, “Lipophilic methylene blue analogues enhance mitochondrial function and increase frataxin levels in a cellular model of Friedreich’s Ataxia,” was published in the journal Bioorganic & Medicinal Chemistry.
A major goal in FA research is to find therapies that increase the levels of frataxin in affected cells.
A class of chemical compounds called methylene violet analogues was shown to have therapeutic potential for neurodegenerative and mitochondrial disorders.
Now, researchers have described a class of methylene blue analogues and assessed their potential for FA treatment. Methylene blue has long been used as a therapeutic agent in several diseases including malaria, cyanide poisoning, methemoglobinemia, and ifosfamide-induced encephalopathy.
Methemoglobinemia is a blood disorder characterized by the formation of an abnormal form of hemoglobin, the molecule that carries oxygen to cells and tissues throughout the body. Ifosfamide-induced encephalopathy is a brain disease caused as a side-effect of treatment with a chemotherapy agent whose active compound is ifosfamide (sold under the name of Ifex, among others).
Additionally, methylene blue “is widely recognized as being neuroprotective in many neurodegenerative diseases such as Alzheimer’s disease,” researchers wrote.
In a fruit fly model of FA, methylene blue was shown to rescue heart defects.
Researchers synthesized seven methylene blue analogues and tested their effects using FA cells, namely lymphocytes, which are cells of the immune system.
Incubation of cells with each methylene blue analogue showed that some of them increased the levels of frataxin and the generation of new mitochondria, the cell’s powerhouses that are affected in FA.
Also, the methylene blue analogues improved mitochondrial function and supported the synthesis of ATP – the cells’ energy currency – in FA lymphocytes, and protected the cells from oxidative stress.
Of the seven analogues tested, analogue No. 5 showed no toxicity to FA cells and was more effective than the original methylene blue.
The mechanisms underlying how methylene blue and the new analogues lead to an increased expression of frataxin remain unknown.
Overall, “improvement in the quality of mitochondria in FRDA patient-derived cells by treatment with MB and the MB analogues appears promising and suggests that more detailed investigation may reveal yet more efficacious compounds,” the study concluded.
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