A low-oxygen environment similar to the air around Mount Everest’s base camp could be key to tackling and even reversing Parkinson’s disease, a new study suggests.
The research, published in the journal Nature Neuroscience, shows that faulty cellular processes in the brain cause a build-up of excess oxygen molecules, leading to Parkinson’s symptoms.
The excess oxygen appears to drive the breakdown of cells in the brain, suggesting that limiting oxygen intake could help slow or reverse symptoms, say researchers from Harvard Medical School.
Parkinson’s patients experience a progressive loss of neurons in the brain, leading to tremors and slowed movements, with the disease affecting over 10 million people worldwide.
Neurons affected by Parkinson’s also tend to accumulate toxic protein clumps called Lewy bodies, with some research suggesting that these clumps interfere with the function of mitochondria, the powerhouse of the cell, .
Anecdotal case studies have shown that people with Parkinson’s seem to fare better at high altitudes.
“Based on this evidence, we became very interested in the effect of hypoxia on Parkinson’s disease,” said study author Fumito Ichinose.
“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… That raised the question: Could the same be true in more common neurodegenerative diseases like Parkinson’s?” said Vamsi Mootha, another author of the study.
In the research, scientists induced Parkinson’s-like conditions in mice by injecting them with clumps of the α-synuclein proteins that seed the formation of Lewy bodies.
They then split the mice into two groups – one breathing normal air with 21 per cent oxygen, and the other continuously housed in chambers with 11 per cent oxygen, comparable to living at an altitude of about 4,800 metres (16,000 ft).
Researchers found that just three months after receiving the α-synuclein protein injections, mice breathing normal air had high levels of Lewy bodies, dead neurons, and severe movement problems.
On the other hand, the mice kept in low-oxygen conditions didn’t lose any neurons and showed no movement problems, despite developing Lewy bodies.
The results show that while hypoxia couldn’t stop the formation of Lewy bodies, it was protecting neurons from the damaging effects of these protein clumps.
Researchers hope the findings could serve as a new way to interpret and treat Parkinson’s without targeting α-synuclein or Lewy bodies.
Scientists also found that the low-oxygen treatment still worked even when hypoxia was introduced six weeks after the injection, when symptoms were already appearing.
After six weeks, the mice’s motor skills rebounded, their anxiety-like behaviours faded, and the loss of neurons in the brain stopped, researchers found.
When scientists analysed the brain cells of the mice, they discovered that mice with Parkinson’s symptoms had much higher levels of oxygen in some parts of the brain than control mice and those that had breathed low-oxygen air.
They suspect the excess oxygen likely resulted from mitochondrial dysfunction.
With the damaged cell powerhouses unable to use oxygen efficiently, oxygen was building up to damaging levels, researchers say.
“Too much oxygen in the brain turns out to be toxic. By reducing the overall oxygen supply, we’re cutting off the fuel for that damage,” Dr Mootha said.
Scientists are working on “hypoxia in a pill” drugs which mimic the effects of low oxygen to treat disorders stemming from mitochondrial dysfunction.
But while the results are encouraging, researchers caution that more research is needed before the findings can be directly used to treat Parkinson’s in humans.
“It may not be a treatment for all types of neurodegeneration…but it’s a powerful concept – one that might shift how we think about treating some of these diseases,” Dr Mootha said.
