New research at the Stanford University School of Medicine found that an existing, FDA-approved form of asthma medication called formoterol improved cognitive functions in a mouse model of Down syndrome. Science Daily reports that by activating certain adrenergic receptors, a high dosage of the drug fortified nerve connections in the hippocampus among lab mice engineered to exhibit cognitive impairment mirroring that of individuals with Down syndrome.
According to the study, the mice treated with formoterol displayed improvement in “contextual learning” – the process whereby the brain weaves together spatial and sensory data to establish a model, or context, of the environment that is being navigated.
Contextual learning, along with memory function and attention span, are centered in a brain structure known as the hippocampus, which largely depends on a healthy supply of a specific neurotransmitter called norepinephrine. The cognitive dysfunction in individuals suffering from Down syndrome is a result of impaired hippocampal function, and scientists have previously linked such disabilities to deterioration of the cerebral center that manufactures these neurotransmitters.
The experiment targeted a specific adrenergic receptor known as beta-2, which the norepinephrine relies on when sending its signal.
"This study provides the initial proof-of-concept that targeting beta-2 adrenergic receptors for treatment of cognitive dysfunction in Down syndrome could be an effective strategy," said Dr. Ahmed Salehi, the study’s lead author.
After first introducing a compound that blocked the action of the beta-2 receptors, the scientists then administered formoterol to the subjects. Beyond improvements in contextual learning and hippocampal activity, they noted more synapses as well as more complex neural structures within the area.
"The fact that such a short period of giving medication can make these neurons much more complex is very interesting," Salehi said.
Today, Down syndrome affects about 400,000 in the United States and 6 million worldwide. The condition entails various kinds of complications, including slow learning among children and Alzheimer’s-type pathology in adults. People with Down syndrome are also more prone to heart disease.
Further testing is still needed to determine whether the drug could be a feasible component of a cognitive treatment program, as the dose used in the lab mice were many times higher than that used for treating asthma in humans.
A treatment program designed to rectify cognitive dysfunction in children suffering from the debilitating condition is not without its opponents. Parents often raise concerns that methods targeting such aspects would potentially alter key attributes of the child’s personality.
However, Dr. Salehi stresses that the goal is simply to facilitate learning. "Our aim is to enable these children to do better in school. It is absolutely not to change their personalities or the way they react to society. Changing a child's personality would be much more complicated than activating a subgroup of receptors in the brain.”
The study will be published in Biological Psychiatry.