Down syndrome, also known as trisomy 21, is among the most frequent genetic causes of intellectual disability. Much research has been focused on improving the intellectual function of those individuals. A new study holds promise for significantly improving cognition in individuals with Down syndrome. Researchers at Johns Hopkins University School of Medicine have discovered a compound that can markedly bolster mental function in mice with a condition very similar to Down syndrome. The results were published in the September 4 issue of Science Translational Medicine.
The researchers conducted their study on Ts65Dn mice, which exhibit some major brain structural and behavioral characteristics of Down syndrome, including reduced size and cellularity of the cerebellum and learning deficits associated with the hippocampus. They found that a single treatment to newborn mice with the Sonic hedgehog pathway agonist SAG 1.1 (SAG) results in normal cerebellar morphology in adult mice. In addition, SAG treatment at birth prevented hippocampal deficits that occur in untreated adult Ts65Dn mice. They noted that this treatment resulted in behavioral improvements and normalized performance in the Morris water maze task for learning and memory. The Morris water maze test is an experiment that involves placing the mice in a pool of water and seeing how long it takes them to escape using a platform hidden below the water’s surface. It measures the rodents’ spatial learning and memory capabilities, which are primarily controlled by the hippocampus. In addition, the researchers found that SAG treatment improved physiological measures associated with memory.
The study authors concluded that the results of their study confirm an important role for the hedgehog pathway in cerebellar development and raise the possibility for its direct influence in hippocampal function. They noted that the positive results from the study suggest a possible direction for therapeutic intervention to improve cognitive function for those with Down syndrome. They caution that the sonic hedgehog agonist has yet to be proven effective in humans with Down syndrome; thus, future research is needed to determine exactly how the injection improved the mice’s cognitive abilities and whether the agonist has any side effects. However, at present, the investigators are hopeful that the treatment can be applied to—and will benefit—individuals with Down syndrome.