A low-oxygen environment, akin to the thin air found at Mount Everest’s base camp, has been shown to protect the brain and restore movement in mice with a Parkinson’s-like disease. This groundbreaking study, conducted by scientists at Harvard Medical School, Massachusetts General Hospital, and the Broad Institute of MIT and Harvard, was published on August 6 in Nature Neuroscience.
The research suggests that cellular dysfunction in Parkinson’s disease leads to an accumulation of excess oxygen in the brain, which subsequently fuels neurodegeneration. The study’s findings hint that reducing oxygen intake could potentially prevent or even reverse Parkinson’s symptoms. However, researchers caution that while these results are promising, more research is needed to determine if the same mechanism applies to humans.
“The fact that we actually saw some reversal of neurological damage is really exciting,” said co-senior author Vamsi Mootha, HMS professor of systems biology and medicine at Mass General and an institute member of the Broad Institute.
Co-senior author Fumito Ichinose, the HMS William T. G. Morton Professor of Anaesthesia at Mass General, added, “The results raise the possibility of an entirely new paradigm for addressing Parkinson’s disease.”
A Long-Standing Link Explored
Parkinson’s disease affects over 10 million people worldwide, causing the progressive loss of neurons in the brain, which leads to tremors and slowed movements. The neurons affected by Parkinson’s gradually accumulate toxic protein clumps called Lewy bodies, potentially interfering with the function of mitochondria—the tiny powerhouses of cells.
Anecdotal evidence suggests that people with Parkinson’s may fare better at high altitudes. Additionally, long-term smokers, who have elevated levels of carbon monoxide and lower oxygen levels in their tissues, appear to have a lower risk of developing the disease.
The study builds on a decade of research by Mootha and others into hypoxia—the condition of having lower than normal oxygen levels in the body or tissues—and its unexpected ability to protect against mitochondrial disorders.
“We first saw that low oxygen could alleviate brain-related symptoms in some rare diseases where mitochondria are affected, such as Leigh syndrome and Friedreich’s ataxia,” Mootha said. “The findings raised the question of whether the same could be true in Parkinson’s.”
A New Paradigm for Parkinson’s
Mootha and Ichinose employed a well-established mouse model of Parkinson’s, in which animals are injected with alpha-synuclein proteins that seed the formation of Lewy bodies. The mice were divided into two groups: one breathing normal air containing 21 percent oxygen, and the other breathing air with 11 percent oxygen, comparable to living at an altitude of about 16,000 feet.
Three months after receiving the alpha-synuclein protein injections, the mice breathing normal air exhibited high levels of Lewy bodies, many dead neurons, and severe movement problems. Conversely, the mice breathing low-oxygen air still developed abundant Lewy bodies but did not lose any neurons and showed no signs of movement problems.
Implications and Future Directions
While the study’s results are promising, the researchers emphasize that it’s too early to translate these findings into treatment recommendations for people with Parkinson’s. Unsupervised breathing of low-oxygen air can be dangerous and may even worsen the disease. However, if the findings are confirmed in humans, they could lead to new treatment strategies, such as drugs that mimic the effects of low oxygen.
The announcement comes as researchers continue to explore innovative approaches to treating Parkinson’s disease. The potential for hypoxia-based treatments represents a significant shift in understanding and addressing the disease’s progression.
As the scientific community awaits further research, the study’s findings offer a glimmer of hope for new therapeutic avenues that could one day improve the lives of millions affected by Parkinson’s disease worldwide.
