Scientists design a new type of medication that imitates the physiological advantages of breathing in a slim “mountain air”.
Continuous low-oxygen provided by a daily pill could prove the backup of people with people metabolic diseasesLike Leigh syndrome.
The new medication, called hypoxystat, has extended the life of mice with too much oxygen in their brain up to 4 times, reports an American team from Gladstone Institutes, the University of California San Francisco and the Pharmaceutical Society Maze Therapeutics .
In their experience of proof of concept, the drug worked even when it is given to the mice at a late neurodegeneration stage, where the brain lesions are extended and certain animals are on the verge of death. Advanced damage has been reversed and movement, muscle weakness and loss of coordination have been improved.
Leigh syndrome is a rare and progressive disease where mitochondria cannot use the oxygen of the body fairly quickly. The accumulation of oxygen in the tissues can lead to damage and ultimately cell death. Children with Leigh syndrome often die During the first years of life. About 20 percent only are 20 years old.
Typically, All except 2% inhaled oxygen is found in body mitochondria – famous as the “power” of the cell because of its ability to use oxygen for energy production. But in high altitude regions, the body moves so that oxygen is Not so easily delivered From blood circulation to tissues.
In a revolutionary 2016 experienceResearchers discovered that for Leigh Syndrome’s Mouse Mouse models, living in a low oxygen -content environment prevents brain lesions; It also. Other studies on mice in 2017 And 2019 confirmed these remarkable results.
It is not clear if humans with Leigh syndrome react in the same way to the low oxygen content. But the biochemist Isha Jain of the University of California San Francisco (UCS) and his colleagues already explore a means of imitating these pharmaceutically.
Unlike sleeping in a hypobar room, as some athletes do during training for high altitude events, a medication that encourages the body to work as it could engage in the mountains could operate almost all day, letting A free person to go as usual business, inside or outside.
“It is not practical for each patient with this disease to move to the mountains”, ” said Jain, an author on the three articles as well as this study.
“But this medication could be a controlled and sure way to apply the same advantages to patients.”
Jain was previously consultant for Maze Therapeutics, who sponsored this hypoxystat study, and she has patents related to hypoxia therapy.
She and her colleagues have hypothesized that by ensuring that red blood cells carry more oxygen in the bloodstream, As they do in high altitude environmentsThe amount of oxygen unloaded in the body tissues would be reduced.
In 2017, researchers find A medication, called GBT-440 or Voxelotor, which increases the affinity of hemoglobin from the protein of red cells to bind to oxygen.
When Jain and his team, led by the biochemist Skyler Blume, incubated human red blood cells with GBT-440, they noticed that the cells increased their affinity for hemoglobin by 75%.
Enharded by their results, the researchers found another compound like GBT-440 and named Hypooxystat.
Mouses with Leigh syndrome that have been treated with hypoxystat showed a significant reduction in brain lesions, shown by green markers of lesions in the image below.
Even in subsequent stages of the disease, a daily dose of this drug has considerably prolonged the lifespan of the mouse and inverted significant damage in the brain.
“This ability to reverse advanced pathology positions hypoxystat and related compounds as promising therapeutic candidates for mitochondrial diseases, where early diagnosis and intervention are often difficult”, the authors of study conclude.
The research team now explores a second generation version of the hypoxystat which could better result in primates or human models Clinical trials.
“Gas therapies for the disease are really unique, and being able to bottle them in medication is a new unusual concept”, ” said Jain. “We are delighted to see where this promising strategy takes us.”
The study was published in Cell.