Study finds CRISPR-Cas9 technology can lessen autism symptoms in mice

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A study published Monday found that the CRISPR-Cas9 DNA-cutting enzyme can be used to lessen some symptoms of autism in mice with fragile X syndrome, or FXS, which is considered a common genetic cause of autism spectrum disorder.

Researchers from UC Berkeley and University of Texas at San Antonio applied the CRISPR-Gold method, which uses gold nanoparticles to deliver the Cas9 enzyme to the brain in order to edit the gene for a neurotransmitter receptor and reduce repetitive behaviors typical of FXS. Hye Young Lee, the lead researcher and an assistant professor of physiology at UT San Antonio, said this study marks the first time a nonviral delivery of the Cas9 protein into the brain showed a reduction in autism symptoms.

“Viral delivery of the Cas9 protein can potentially cause off-target effects, cytotoxicity and immune reactions,” Lee said. “I’m excited about gene mutation because it’s a simple way to treat a single gene and it can have significant effect on treatment development.”

Lee said autism spectrum disorder is behaviorally defined, which makes it difficult for researchers to develop a drug or other treatment. Gene editing can target the known genetic causes of autism, such as FXS, wherein neurons become very excited and cause repetitive behaviors and social deficits.

The repetitive behaviors exhibited by the mice were digging and periodic jumping. Study contributor and campus bioengineering professor Niren Murthy said the behaviors were caused by an overactivation of a specific neurotransmitter receptor —  metabotropic glutamate receptor 5, or mGluR5 — which the Cas9 injection targeted.

“We injected the Cas9 protein into the striatum, which is the part of the brain involved in habit formation, and were able to rescue those excessive behaviors in the mice,” Lee said.

The technique can potentially be used to treat other neurological differences such as Huntington’s disease and epilepsy “if the gene target is known very well,” according to Lee.

Despite positive reactions to this technique, some have reservations about the possible effects of gene editing. A 2017 Time magazine article, “How Gene Editing Could Ruin Human Evolution,” argued that “there are no superior genes” and that using gene editing to treat autism can disrupt evolutionary processes. The article claimed that evolution does not progress to an ideal model and that nature does not dictate the way a gene should function.

Ross Wilson, a project scientist at the Innovative Genomics Institute, works with CRISPR-Cas9 delivery and said the study is a “really promising advance for the field.” He added that the ability to make a genetic change in brain cells of mice and see behavioral change as a result signifies that something similar could result in a human patient.

“It demonstrates that if we are able to deliver something to the brain of a patient and get it into more cells, we can correct more neurological diseases,” Wilson said.

Lee said the next steps after this study will be to target a wider brain region, move on to larger animals to ensure that the technique works for other species and test the technique’s safety before human clinical trials. She said the conditions of this study were safe but that the technique must be tested for side effects such as personality changes.

“I’m desperately wanting to develop a treatment for autism, and I’m hopeful that gene editing using CRISPR will provide another option for people with autism,” Lee said.

Contact Amanda Bradford at [email protected] and follow her on Twitter at @amandabrad_uc.