Asthma Meds May Boost Cognition in Down Syndrome Patients
Asthma medication may help improve cognition in people with Down syndrome, a new study suggests.
Stanford researchers found that the FDA-approved asthma drug formoterol improved cognitive function in a mouse model of Down syndrome.
The findings revealed that formoterol strengthened nerve connections in the hippocampus, a brain region used for spatial navigation, attention and memory formation. Researchers also found that the asthma medication improved contextual learning, in which the brain integrates spatial and sensory information.
Researchers explain that both hippocampal function and contextual learning, which are impaired in Down syndrome, depend on the brain having an ample supply of the neurotransmitter norepinephrine. The neurotransmitter norepinephrine sends its signal through several types of receptors on neurons, including a group called beta-2 adrenergic receptors.
"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," study senior author Dr. Ahmed Salehi, a clinical associate professor of psychiatry and behavioral sciences, said in a news release.
Previous Down syndrome research revealed deterioration of the brain center that manufactures norepinephrine in both people with Down syndrome and its mouse model. In a previous study, Salehi and his team found that giving a norepinephrine precursor could improve cognition in a mouse model genetically engineered to mimic Down syndrome.
In the new study, Salehi and colleagues refined this work by targeting only one group of receptors that respond to norepinephrine: the beta-2 adrenergic receptors in the brain. Researchers first gave the mice a compound that blocks the action of beta-2 adrenergic receptors outside the brain. Afterwards, they gave the mice formoterol, a drug that can partially cross the blood-brain barrier and that was already known to activate beta-2 adrenergic receptors.
The findings revealed that mice given the asthma drug showed significant improvement on a standard test of contextual learning. The study also revealed that the hippocampus of mice given formoterol had more synapses and a more complex structure of dendrites.
"The fact that such a short period of giving medication can make these neurons much more complex is very interesting," Salehi said, adding that mice in the study received the drug for a maximum of two weeks.
Researchers said the next step is to see whether formoterol or other drugs that activate the same receptors might be appropriate treatments for people with Down syndrome. Salehi and his team noted that the dose used in the experiment was many times higher than that used for asthma treatment, so it is not known whether it is safe. However, a lower dose might work, or other drugs that affect beta-2 adrenergic receptors might be safer and more effective in humans.
The findings are published in the journal Biological Psychiatry.