Epigenome editing could lead to treatment of brain abnormalities in WAGR syndrome

Using cell lines contributed by participants in the National Institutes of Health (NIH) study of Aniridia, WAGR syndrome, and 11p Deletions (2006-2014), researchers at the Johns Hopkins University School of Medicine have developed an epigenome editing approach that reversed a brain abnormality that is common in individuals with WAGR syndrome. The technique used in this research is unique because it changes the epigenome which regulates the gene, but doesn’t change the actual genetic code.

The technique was successful in mice, and could prove useful in humans in the future.

The targeted gene, called C11orf46, is a regulator for brain development. In the typical brain, the job of this gene is to switch a direction- sensing protein called Semaphorin 6a from the “off” position to “on” mode, so it can guide the long fibers that grow out of newly formed neurons. These neurons then go on to form the corpus callosum, a bundle of fibers that joins the two hemispheres of the brain. The corpus callosum helps to control movement and feeling on opposite sides of the body, and also helps the brain to process sensory information and language.

Defects in the C11orf46 gene are linked to poor development of the corpus callosum, which can result in seizure disorders, impaired physical coordination, and impaired visual, auditory, or sensory integration.

For this study, the researchers used a modified CRISPR genome editing system. The editing process allowed the researchers to bind and turn down the gene in mice brains. The process allowed the researchers to bundle the neuron fiber, which in turn restored normal brain functioning in the mice.

“Although this work is early, these findings suggest that we may be able to develop future epigenome editing therapies that could help reshape the neural connections in the brain, and perhaps prevent developmental disorders of the brain from occurring,”
Atsushi Kamiya, M.D., Ph.D., Associate Professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.

Typical human brain VS. Brain of child with WAGR syndrome
Photo: Johns Hopkins University School of Medicine

For additional information, visit the following sites:

What is Epigenetics?
https://ghr.nlm.nih.gov/primer/howgeneswork/epigenome

What is the Corpus Callosum?
https://www.neuroscientificallychallenged.com/blog/know-your-brain-corpus-callosum

What is CRISPR?
https://www.livescience.com/58790-crispr-explained.html

National Institutes of Health (NIH) study of Aniridia, WAGR syndrome, and 11p deletions (2006-2014)
https://wagr.org/clinical/national-institutes-of-health/