3rd December 2023 – (Beijing) Scientists from Shanghai have developed an injection that could potentially reverse autism symptoms through gene-editing within the brain. The pioneering treatment has demonstrated encouraging results in test trials involving mice.
The research group engineered a genome editing system capable of modifying the DNA in mice afflicted with a mutation associated with autism spectrum disorder (ASD). Following the injection of the editing system, a marked decrease in ASD-related behaviour was observed.
This groundbreaking discovery, detailed in the Nature Neuroscience journal on 27th November, suggests that the novel treatment could have applications beyond ASD, potentially benefitting patients with other genetic neurodevelopmental disorders.
ASD is a far-reaching disorder, affecting approximately 1% of the global population. It is particularly prevalent in the United States, where one in every 36 children is diagnosed with the condition, according to the US Centres for Disease Control and Prevention (CDC). ASD can significantly impact an individual’s ability to communicate and interact, often leading to repetitive behaviours and intense interests.
To explore the potential of genomic editing in treating ASD, the scientists generated mice with mutations in the MEF2C gene, a variant strongly associated with the disorder. Mutations in this gene are thought to cause developmental deficits, speech problems, repetitive behaviours, and epilepsy.
Male mice with the mutation exhibited lower levels of the MEF2C protein in the brain, along with symptoms mirroring ASD-like hyperactivity, social interaction difficulties and repetitive behaviour.
Earlier this month, the UK became the first country to approve a CRISPR-Cas9 gene editing therapy for patients with blood conditions such as sickle cell disease. While CRISPR-based systems perform gene editing by severing the DNA double strand, which cells repair once editing is complete, this process can lead to unintended mutations.
To mitigate this risk, the Chinese researchers employed a single-base editing system, named AeCBE, capable of operating on individual DNA base pairs without creating any cuts.
According to Li Dali, a professor of Life Sciences at East China Normal University, this marks the first successful treatment of mice with ASD-related mutations using base editing in the brain.
The delivery of the system into the brain required bypassing the blood-brain barrier, a group of cells that strictly regulates the entry of molecules into the brain. The research team surmounted this obstacle by attaching their editing system to an adeno-associated virus vector able to cross into the brain.
Administered to mutant mice via a single tail vein injection, the combined editing system and virus vector were evaluated a few weeks later. The treatment successfully restored MEF2C protein levels in several brain regions and reversed the behavioural abnormalities in MEF2C-mutant mice.
The researchers found that their editors were able to perform repairs across the brain with a 20% accuracy rate, sufficient to raise levels of the MEF2C protein.
Despite ASD’s complex nature, this study provides a roadmap for using base editing to treat neurodevelopmental disorders, according to researcher Chen Jin and his student Zhu Junjie at ShanghaiTech University.
As the technology expands and costs diminish, treatment using base editing could become more widespread. “Individualised gene editing therapy could become feasible and affordable for patients in the near future,” the researchers stated.
While the disorder may not be caused by a single nucleotide variation, as it was for the mice in the study, but rather more complex mutations that would be difficult to edit, this development is a significant step forward.