Chronic, continuous 11% O2 breathing once advanced neurological disease has started can rapidly reverse ataxia, showed a new study in a mouse model of Friedreich ataxia (FA).
The study is published in the journal Human Molecular Genetics.
Read more about FA diagnosis
“Our studies showcase both the promise and limitations of candidate hypoxia-inspired regimens for FA and underscore the need for additional preclinical optimization before future translation into humans,” the authors wrote.
The study also showed that a daily, intermittent hypoxia regimen of 11% O2 for 16 hours per 21% O2 for 8 hours had no benefit and was even harmful, resulting in high cardiac stress and accelerated mortality.
Finally, a mild regimen of chronic hypoxia, or 17% O2, had modest benefits and delayed the onset of ataxia.
It was already known that oxygen could modify the pathogenesis of FA, and previous research in a mouse model of FA has shown that chronic, continuous normobaric hypoxia, or 11% FIO2, prevented ataxia and neurological disease, the researchers noted.
In the present study, a team of researchers led by Vamsi Mootha, MD, from Harvard Medical School in Boston, Massachusetts, evaluated the effect of 7 ‘hypoxia-inspired’ regimens in the FA mouse.
Their ultimate aim was to design a safe, practical, and effective regimen that could be translated into the clinic.
“Based on [our] findings, we emphasize the need for additional pre-clinical evaluation of hypoxia and hypoxia-inspired regimens before proceeding to testing in FA patients,” the researchers wrote. “Such studies should be worthwhile, especially as we find that initiating hypoxia at advanced timepoints can prevent and even reverse the neurological defects we have assayed.”
FA is a genetic disease caused by a mutation in the frataxin gene, which contains the information necessary to make a protein that controls adenosine triphosphate synthesis and iron homeostasis in mitochondria. Around 1 in 50,000 Americans are affected by FA.
Reference
Ast T, Wang H, Marutani E, et al. Continuous, but not intermittent, regimens of hypoxia prevent and reverse ataxia in a murine model of Friedreich’s ataxia. Hum Mol Genet. Published online June 1, 2023. doi:10.1093/hmg/ddad091
