A new study suggests genetic mutation that helps animals survive at high altitudes may hold the key to repairing nerve damage in multiple sclerosis. The findings reveal a naturally existing pathway that promotes regeneration after nerve damage, and could open new doors for treating MS by leveraging molecules that are already present in the human body. 

The myelin sheath is a protective layer that surrounds nerve fibers in the brain and spinal cord, allowing nerve signals to transmit efficiently. In adults, injuries to the myelin sheath are tied to MS, an autoimmune disease in which the immune system mistakenly attacks and destroys the myelin sheath.

In previous studies, researchers have found that animals living on the Tibetan Plateau — which has an average elevation of 14,700 feet — carry a mutation on a gene called Retsat. Scientists at Songjiang Hospital, affiliated with the Shanghai Jiao Tong University School of Medicine, suspected this mutation helps animals such as yaks and Tibetan antelopes maintain healthy brain function despite chronically low oxygen levels.  

The research team investigated if this mutation could prevent myelin sheath damage. They exposed newborn mice to low-oxygen conditions equivalent to elevations above 13,000 feet for about a week. Mice carrying the Retsat mutation performed significantly better in learning, memory, and social behavior tests than those with the standard version of the gene. Brain analyses also revealed the high-altitude gene mice had higher levels of myelin surrounding their nerve fibers.  

The researchers then examined whether the Retsat mutation could repair myelin sheath damage similar to that seen in MS. They found that in mice carrying the mutation, the myelin sheath regenerated much faster and more completely after injury. The injury sites also had more mature oligodendrocytes, a type of cell responsible for producing myelin. 

Further investigation showed mice with the mutation produced higher levels of ATDR, a metabolite derived from vitamin A, in their brains. The Retsat mutation appeared to increase the enzymatic activity that converts vitamin A into its metabolites, which in turn promotes the production and maturation of myelin-producing oligodendrocytes. When the team gave ATDR to mice with an MS-like disease, their disease severity decreased, and they showed improved motor function. 

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the researchers noted that ATDR is something everyone already has in their body. They argue that the findings suggest there may be an alternative approach that uses naturally occurring molecules to treat diseases related to myelin damage. 

The study was published in the journal Neuron.