Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy, characterized by progressive muscle wasting and weakness and caused by abnormally repetitive DNA segments that are transcribed into toxic molecules of RNA. Instead of ferrying a gene’s instructions for translation into proteins, these RNA molecules accumulate in cells, disrupting cellular machinery.
Rett syndrome (RS) is a rare genetic neurological disorder that affects the way the brain develops, resulting in progressive loss of motor skills and language early in life.
Writing in the June 29, 2022 online issue of Science Translational Medicine, researchers at University of California San Diego School of Medicine used three-dimensional brain organoids — self-organized tissue grown from stem cells that mimics neurological functions — to discover fundamental similarities between DM1 and RS, and perhaps therapeutic opportunities.
“We turned to 3D brain organoids that simulate the developing human cortex to study the effects of the CTG repeat expansion on neuronal processes,” said first author Kathryn Morelli, PhD, a fellow in the lab of senior author Gene Yeo, PhD, professor of cellular and molecular medicine at UC San Diego School of Medicine.
“It’s a model that can be made from induced pluripotent stem cell lines from real DM1 patients that carry these toxic RNA aggregates. It mimics cortical development in utero.”
Unlike other types of muscular dystrophy, patients with DM1 often exhibit progressive neurocognitive symptoms, with learning and social impediments that can appear similar to autism spectrum disorders. Recent clinical data has shown that the higher the number of inherited DNA repeats, the earlier the onset of symptoms — and the greater the impact of the disease on the central nervous system.
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