AHC is a rare neurological disorder affecting 1 in a million people<\/a>. Symptoms, which usually begin before the age of 18 months, include weakness and paralysis in one or both sides of the body, muscle stiffness and, in some cases, seizures.<\/p>\n Current treatments help with symptom management but there is no known cure for AHC.<\/p>\n The researchers consisted of a team from the Rare Disease Translational Centre, the Broad Institute and the not-for-profit, RARE Hope.<\/p>\n Mice models were previously developed<\/a> by Markus Terrey and Cathleen Lutz, vice president of the Rare Disease Translational Centre.<\/p>\n \u201cFive years ago, people would have thought that going into the brain of a living organism and correcting DNA was science fiction. Today, we know this is doable,\u201d says Terrey, who co-led the study.<\/p>\n \u201cDoing this directly in the brain of a living organism is scientifically fascinating. You can go into the brain, fix the mutation, and have the cells corrected for the rest of their life.\u201d<\/p>\n The team used prime editing to correct 85% of the faulty gene mutations in the brain.<\/p>\n \u201cThis level of editing efficiency in the brain is really quite remarkable,\u201d says Lutz.<\/p>\n Prime editing<\/a> uses CRISPR technologies and reverse transcriptase enzymes to create new single strands of DNA that can be inserted into existing DNA sequences.<\/p>\n The correction restored normal protein function allowing for a reduction in seizures and motor skill improvement. It also extended the lifespan in mice.<\/p>\n \u201cUp until this point, we didn\u2019t know if this was a disease that could be rescued postnatally,\u201d says Nina Frost, a co-author of the study and mother of a daughter with AHC. \u201cTo see data that showed not just molecular correction in cells, but a functional rescue in mouse behavior, was an incredibly exciting moment.\u201d<\/p>\nMarkus Terrey, neuroscientist at JAX, co-led the pioneering study that corrected AHC-causing mutations directly in the brain of mice. Credit: The Jackson Laboratory.<\/p>\n
Illustration of gene editing in neurons. Credit: The Jackson Laboratory.<\/p>\n
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\n<\/a><\/p>\nCathleen (Cat) Lutz, vice president of the Rare Disease Translational Center at JAX, emphasized the broader implications of the breakthrough, calling it a major step toward personalized therapies for rare genetic disorders. Credit: The Jackson Laboratory.<\/p>\n