Autism is a neurodevelopmental disorder characterized by language deficits, impaired social interaction, and repetitive, restricted behaviors, often presenting with intellectual disability in genetic syndromes. With an incidence of 1 in 68 and no mechanism-based therapeutics available, autism is an area of great unmet need. Several biological models suggest that the condition is strongly correlated with dysregulation of protein synthesis in the synapses of the brain's neurons. Therefore, discovery of drugs that normalize protein translation is a promising therapeutic strategy. Efforts thus far to normalize translation by targeting upstream receptors that induce it (e.g. mGluR5) have failed.
Anima's platform offers a powerful new way to screen for translation-normalizing therapeutics in patient-derived cells using an unbiased high-throughput approach. Such an approach could be used to identify first-in-class, mechanism-based pharmacotherapies for autism.
With our PSM technology, we can visualize the ribosomes broadcasting light pulses as they translate proteins. The top row images show the light glowing in the synapses as the brain of a healthy mice is induced with a learning signal. The left column shows the "before" and the right column the "after" of the learning signal. The synapse lights up in response to the learning signal. In the second row, we can see what happens to a mouse with the autism Fragile X syndrome mutation – almost no light is observed. The synapses stay "in the dark" and indeed, those mice are unable to learn and demonstrate multiple symptoms of Autism. However, in the 3rd row of images, once the mutated gene is restored to normal in a transgenic ("bio-engineered") mice, the light comes back to the synapses in response to the learning signal.
With our platform, we now systematically screen for compounds that normalize the process of protein translation. Such molecules would "bring the lights back-on" by controlling the regulation mechanisms of the synthesis process.