Can CRISPR Treat Autism? Results In Mice Point To Yes
In a pioneering experiment, researchers from Texas and California have reduced the obsessive and repetitive behavior of mice with fragile X syndrome, a form of inherited autism spectrum disorder, using CRISPR-Cas9 gene-editing enzymes that were delivered to brain cells via gold nanoparticles.
The impressive efficacy and apparent safety demonstrated by their results, described in the journal Nature Biomedical Engineering, are poised to open the floodgates for investigations exploring CRISPR’s potential for other neurological diseases, chronic pain, and even addiction.
Traditional CRISPR-Cas9 delivery – employing modified viruses to inject genes encoding the molecular machinery into cells’ genomes – has proven ill-suited for applications in the brain because it is difficult to control the quantity of Cas9 proteins and guiding RNA molecules that are produced. Additionally, the foreign proteins that make up Cas9 are then expressed indefinitely in brain tissue, often inducing a harmful immune response and leading to unintended changes in neural functioning (yikes).
To remedy these issues, UC Berkeley researcher Niren Murthy developed a non-viral CRISPR platform, called CRISPR-Gold, wherein preassembled Cas9-RNA complexes are stuck onto gold nanoparticles. The resulting clusters are then covered with a polymer that enables them to enter cell membranes.
After CRISPR-Gold first proved its promise by successfully modifying genes in diseased muscle cells, Murthy teamed up with lead author Hye Young Lee to test it in a neurological condition. Fragile X syndrome (FXS) represented an ideal first target.
“FXS is the most common inherited form of intellectual disability and a common single-gene form of autism spectrum disorders (ASDs), accounting for ~2.1% of patients,” the authors wrote. “Current drug treatments, such as psychostimulants, antidepressants, and antipsychotics are ineffective because they do not address the underlying [cause] of FXS; they only target individual symptoms.”
In addition to hindered intellectual capacity, humans with FXS display exaggerated repetitive tics and anxiety. Prior to this study, scientists hypothesized that the obsessive behavior patterns characteristic of FXS and other ASDs arise from hyperactivity of a neuron-to-neuron signaling receptor called metabotropic glutamate receptor 5, or mGluR5, but they lacked conclusive evidence. It was also unknown where in the brain this unwanted over-signaling occurred.
Published at Thu, 28 Jun 2018 21:15:00 +0000