Hypoxia slows Parkinson's disease in mice. Scientists report a new direction in therapy.

Scientists from the Broad Institute and Mass General Brigham have discovered that a low-oxygen environment can protect neurons and improve motor performance in a mouse model of Parkinson's disease. This effect was achieved when the animals breathed air similar to that found at high altitude. The authors of the study, published in Nature Neuroscience, believe that the hypoxia mechanism could one day be used to treat humans.

Parkinson's disease affects more than 10 million people worldwide and leads to the gradual loss of neurons responsible for movement control. It is accompanied by tremors, slow movement, and the accumulation of Lewy bodies—toxic clumps of α-synuclein proteins—in the brain.

A team led by Professor Vamsi Mootha and Professor Fumito Ichinose discovered that the disease also leads to excessive oxygen accumulation in certain regions of the brain. This is caused by mitochondrial dysfunction, which stops using oxygen efficiently. "Too much oxygen in the brain is toxic. By reducing the overall oxygen supply, we cut off the fuel for this damage," explains Mootha.

Researchers decided to investigate the impact of exposure to low oxygen levels on the disease. They used a mouse model of Parkinson's disease in which aggregates of the protein α-synuclein are injected into the brain. Some of the animals were kept in normal air (21% oxygen), while others were kept in chambers with reduced oxygen content to 11%—equivalent to an altitude of approximately 4,800 meters above sea level.

The effects were clear. Mice breathing air with lower oxygen levels retained their neuronal loss and maintained normal motor function, even though Lewy bodies continued to form in their brains. Hypoxia didn't stop the formation of protein deposits, but it did prevent them from harming neurons.

Moreover, when hypoxia was introduced only six weeks after the onset of symptoms, the animals also regained some motor function and stopped losing neurons.

Analyses showed that the brains of mice with Parkinson's disease had significantly higher oxygen concentrations than those of healthy animals. Hypoxia reduced these levels, limiting the toxic effects of excess oxygen on nerve cells.

Researchers warn that breathing low-oxygen air on their own, especially periodically, can be dangerous. Instead, they are working on drugs that would mimic the beneficial effects of hypoxia, so-called "hypoxia in a pill." They are already testing this approach in mitochondrial diseases such as Leigh syndrome and Friedreich's ataxia.

While the method may not work for all neurodegenerative diseases, it has worked in several models, including Parkinson's disease and accelerated aging.