Breakthrough Discovery of TMEM63A Gene Offers Hope for Myelin Disorders

Researchers at Oregon Health & Science University (OHSU) have made a significant discovery regarding a gene that plays a crucial role in the formation of myelin, the protective sheath around nerve fibers. Their findings, published on July 22, 2025, in the Proceedings of the National Academy of Sciences, highlight the gene transmembrane protein 63A (TMEM63A) and its implications for treating disorders such as multiple sclerosis and a rare condition known as infantile hypomyelinating leukodystrophy 19 (HLD19).

The discovery sheds light on the genetic underpinnings of HLD19, a disorder that severely impacts brain development in infants, leading to developmental delays and coordination issues due to insufficient myelin. According to Dr. Swetha Murthy, assistant scientist at the OHSU Vollum Institute and senior author of the study, "The hope is that if we understand how this gene facilitates myelination, then we can develop therapies that restore or promote myelin formation — not just for this rare disorder, but also for diseases like multiple sclerosis."

The research team utilized advanced models including mice and zebrafish to investigate the effects of inactivating the TMEM63A gene. They found that such inactivation resulted in early myelination defects that closely resemble the symptoms observed in children affected by HLD19. This discovery not only uncovers the role of TMEM63A in myelin production but also highlights its importance as a mechanosensitive ion channel, which helps cells respond to mechanical stimuli.

Dr. Kelly Monk, co-director and senior scientist at the Vollum Institute, noted, "It’s been known for a long time that myelinating cells use physical cues such as the size of individual nerve fibers when they decide where to form their myelin, but how they sense those cues has remained a mystery. This research helps fill that gap."

Demyelination, a process where myelin is damaged or destroyed, is a key factor in multiple sclerosis, a debilitating condition affecting over 2.8 million people globally, according to the National Multiple Sclerosis Society. Dr. Ben Emery, the Warren Distinguished Professor in Neuroscience Research at OHSU, emphasized the broader implications of this research, stating, "We’ve shown that this gene’s effect on myelin is not only real — it’s conserved across species, including zebrafish and mice."

The team plans to delve deeper into the regulatory mechanisms of TMEM63A and its interactions with other proteins that influence myelin formation. Dr. Murthy expressed optimism about the potential applications of their findings: "We want to understand the exact steps in myelin formation where this gene plays a role — and whether that process can be targeted with drugs. If so, it could reshape how we treat both rare leukodystrophies and more common conditions like MS."

This groundbreaking study exemplifies the collaborative spirit at OHSU, bringing together researchers from various disciplines to tackle complex neurological issues. The research was supported by the McKnight Endowment Fund for Neuroscience, the OHSU Silver Family Foundation, and the National Institute of Neurological Disorders and Stroke under the National Institutes of Health.

As the team progresses, the implications of their work could pave the way for innovative treatment strategies that change the outlook for patients suffering from myelin-related disorders, underlining the importance of genetic research in advancing medical knowledge and therapeutic options.