A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Winter, 2020 | Number 1, Volume 34

Abnormalities in brain cells that produce myelin linked to ASD

A new study shows that people with autism spectrum disorders (ASD) have a cellular abnormality that impairs the production of myelin, the fatty insulation around nerve fibers in the brain. 

BaDoi Phan and colleagues studied mice with a gene mutation that causes a condition known as Pitt-Hopkins syndrome when it occurs in humans. Pitt-Hopkins, which is a rare neurodevelopmental disorder, produces autistic-like symptoms. 

The researchers found that in mice with the mutation, a genetic abnormality disrupts the function of oligodendrocytes, which are cells that control myelin production. They then looked at other mouse models of ASD caused by different mutations associated with autism, and found consistent evidence for abnormalities involving oligodendrocytes. Finally, they identified the same abnormalities in brain tissue from deceased people with ASD who did Abnormalities in brain cells that produce myelin linked to ASD not suffer from Pitt-Hopkins syndrome but had more common forms of ASD. 

Study coauthor Brady Maher says, “Myelination is essential to healthy brain development; it’s a process that begins just before birth and continues throughout the lifespan. If impaired, it leads to abnormal brain development that likely results in communication and behavior challenges associated with ASD.” 

He adds, “It appears that in many people who suffer from ASD, their [oligodendrocytes] are not maturing sufficiently or functioning properly. This suggests they are not producing enough myelin insulation for their neurons, which could profoundly disrupt brain development and electrical communication in the brain.” 

The researchers say that while most researchers studying ASD are investigating problems involving neurons, “These findings offer an alternative to the neurocentric view of developmental disorders and suggest that myelination might be a new therapeutic target for the treatment of ASD.” 

The researchers are now testing compounds that may boost myelination in the brain. Maher says, “Because myelination is a lifelong process it provides a unique therapeutic opportunity that we can tap into throughout the lifespan. Along these lines, we are eager to see whether enhancing myelination in these mice can improve their ASD-associated behaviors. Promising [drug] candidates could then be considered for clinical studies.”


“A myelin-related transcriptomic profile is shared by Pitt–Hopkins syndrome models and human autism spectrum disorder,” BaDoi N. Phan, Joseph F. Bohlen, Brittany A. Davis, Zengyou Ye, Huei-Ying Chen, Brent Mayfield, Srinidhi Rao Sripathy, Stephanie Cerceo Page, Morganne N. Campbell, Hannah L. Smith, Danisha Gallop, Hyojin Kim, Courtney L. Thaxton, Jeremy M. Simon, Emily E. Burke, Joo Heon Shin, Andrew J. Kennedy, J. David Sweatt, Benjamin D. Philpot, Andrew E. Jaffe, and Brady J. Maher, Nature Neuroscience, February 3, 2020 (free online). Address: Andrew Jaffe, [email protected], or Brady Maher, [email protected]

—see also— 

“New study links autism to specific cell, paves way for potential approach to treatment,” news release, Lieber Institute for Brain Development, February 3, 2020.