The potential of genome-editing techniques, such as CRISPR/Cas9, to alleviate disease burden has ignited the imagination for thousands of researchers looking for new therapeutic strategies. Scientists were very quickly able to show that this gene-altering technique could eliminate disease-causing mutations within a variety of tissues in vitro. More recently, CRISPR is being positioned to help treat patients directly, with clinical trials in humans already under way in China and soon to begin in the U.S. Yet, no current clinical trials feature drugs made using the technique for the treatment of neurodegenerative diseases.

Now, a group of investigators led by scientists at Emory University is hoping to open up new avenues of neurodegenerative research and rapidly move toward human trials after the release of their new findings. The research team showed that the CRISPR/Cas9 system could snip part of a gene that produces toxic protein aggregates in the brains of 9-month-old mice used as a model for Huntingtons disease. Moreover, the scientists noted that when they looked at the brain region where the vector was applied, some weeks later, the aggregated proteins had almost disappeared. Amazingly, the motor abilities of the mice had improved, although not to the level of control mice.

Findings from the new study were published today in the Journal of Clinical Investigation through an article entitled, CRISPR/Cas9-mediated gene editing ameliorates neurotoxicity in mouse model of Huntingtons disease.

Huntington's disease is caused by a gene encoding a toxic protein (mutant huntingtin or mHTT) that causes brain cells to die. Symptoms commonly appear in mid-life and include uncontrolled movements, balance problems, mood swings, and cognitive decline. The mice used in the current study have a human mHTT gene replacing one of the mouse huntingtin genes. In these mice, motor problems and aggregated mHTT can be observed around the age of 9 months.

We report that permanent suppression of endogenous mHTT expression in the striatum of mHTT-expressing mice (HD140Q-knockin mice) using CRISPR/Cas9-mediated inactivation effectively depleted HTT aggregates and attenuated early neuropathology, the authors wrote. The reduction of mHTT expression in striatal neuronal cells in adult HD140Q-knockin mice did not affect viability, but alleviated motor deficits. Our studies suggest that nonallele-specific CRISPR/Cas9-mediated gene editing could be used to efficiently and permanently eliminate polyglutamine expansion-mediated neuronal toxicity in the adult brain.

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CRISPR Reverses Huntington's Disease in Mice - Genetic Engineering & Biotechnology News

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