'Hypoxia in a Pill' Eases Brain Disorders in Mice
Get the Health newsletter
Daily health & science — research, biotech, public health, the studies worth knowing. Free.
- Vamsi Mootha and colleagues at Massachusetts General Hospital combined osivelotor, originally developed for sickle cell anaemia, with PT2399 to create a "hypoxia in a pill" that mimics high-altitude, low-oxygen effects on the brain.
- The pill more than doubled survival in mice with Leigh syndrome (from roughly 62 to 158 days), halted further declines in strength and coordination in Friedreich's ataxia models, and improved coordination and balance in Parkinson's disease models.
- Osivelotor alters haemoglobin to grip oxygen more tightly, while PT2399 blocks the HIF-2α protein to prevent the dangerous overproduction of red blood cells that osivelotor would otherwise trigger.
- Mootha proposes the treatment may work by reducing excess oxygen that damages cell components, since all three studied conditions are partly characterized by damaged mitochondria that he says may fail to consume oxygen properly.
- Pfizer pulled Oxbryta, a drug from the same class as osivelotor, in 2024 because its benefits didn't outweigh its risks; Mootha's team is now planning human safety trials for the osivelotor-PT2399 combination.
- Gordon Mitchell at the University of Florida cautioned that mice cut metabolism in low oxygen far more readily than humans, while Kamilla Miskowiak at the University of Copenhagen called the pill format "much more feasible" than masks or hypoxia chambers.
Why it matters: Massachusetts General Hospital's mouse proof-of-concept across Parkinson's, Friedreich's ataxia, and Leigh syndrome (where survival more than doubled) opens a pill-based path where hypoxia chambers and masks were the only options. Mouse metabolism differences and the 2024 safety withdrawal of Oxbryta from osivelotor's drug class temper expectations ahead of the team's planned human safety trials.
