These findings are important for investigating the use of low oxygen levels as a potential treatment, however this research is still a long way from clinical application. Limitations were identified in the study which may affect its clinical use, including the finding that brain damage was only reversed in mice that continuously breathed low levels of oxygen. This would be unrealistic for patients and so further work is required to determine if this kind of treatment could be provided in a safe and practical way. Furthermore, supplementary oxygen is often vital in the care of patients with Mitochondrial Disease and these findings do not suggest patients should change existing care regimes which may include supplemental oxygen, without prior consultation with their clinician.
This study looked at mice raised in a low oxygen environment (11% compared to the usual 21%) as well as the effect of moving mice born in a normal environment into a low oxygen environment (which would be more practical for potential treatment).
Mice born in a low oxygen environment (11%) showed no brain damage after 250 days of age, compared to those raised in normal oxygen which showed brain damage before 60 days. In addition, the low oxygen mice lived 270 days (average) compared to only 58 days (average) for mice breathing normal oxygen levels.
Researchers also noted that moving mice from a normal oxygen environment into one with low oxygen appeared to improve brain damage within five days and increased survival, with most of these mice still alive after 210 days — proving that hypoxia can not only prevent, but may also reverse, brain damage in mice with advanced neurological disease.
Researchers also looked at whether it was necessary to continually be in a low oxygen environment to gain any benefit, or if they could get the same results by only providing this for a certain number of hours a day. They tried some mice on low oxygen for 10 hours a day, but unfortunately they found that this did not prevent brain damage developing.
Researchers also tested whether the low oxygen mice who had shown improvement, could be moved to normal oxygen and maintain the positive effects, but unfortunately this change sped up the disease and eventual death - all demonstrating that this potential therapy would have to be continuous to provide benefit.
The study’s co-senior author Dr Vamsi Mootha said in a news release ‘Some of our ongoing work is aimed at determining whether hypoxia therapy will generalize to other models of mitochondrial disease. The results of these studies will help in our design of future translational studies.” He added: “We’re also working to try and identify other, more practical hypoxia regimens that may be effective. Our vision is to be able to offer patients and their families a therapy that not only halts but heals disease, but we’re still only working in animal models. We’re not there yet, but we’ve got all hands-on deck to push this concept forward.’