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A newly published study funded in part by DSRTF shows that an FDA-approved asthma drug already in use improves cognitive function in a mouse model of Down syndrome, providing evidence in support of a new therapeutic target, the beta-2 andregenic receptors in the hippocampus.
The drug, a bronchodilator called formoterol, was shown in the study to strengthen nerve connections in the hippocampus, a brain center used for spatial navigation, paying attention and forming new memories, the study said. It also improved contextual learning, in which the brain integrates spatial and sensory information. A high dosage of the drug was administered over a period no longer than two weeks, resulting in notable improvements in the mice’s neuronal structures. “The fact that such a short period of giving medication can make these neurons much more complex is very interesting,” said Stanford University’s Ahmad Salehi, MD, Ph.D., the study’s lead author and a DSRTF grant recipient.
Salehi called the study, published July 2 in Biological Psychiatry, an “initial proof-of-concept,” cautioning that the dose he and his colleagues used was higher than that used in asthma treatment and cannot be safely adminstered to human patients without the risk of significant side effects. Nonetheless, these results hold great promise for new classes of drugs to target this receptor, with the goal of improving cognition in people with Down syndrome.
DSRTF is continuing support for this exciting research, and will provide updates on its progress.
RDS has been sharing progress from the laboratory of Dr. Ahmed Salehi, an RDS grantee.
Now, a recently published news release describes how the existing FDA-approved asthma medication, formoterol, improved cognitive function in a mouse model of Down syndrome, through improved contextual learning. Strengthened nerve connections in the hippocampus are cited.
The laboratory's research has indicated that increasing the levels of the neurotransmitter norepinephrine(NE), using mouse models, could significantly improve cognitive function. RDS grants have supported studies investigating the potential for lower doses of L-DOPs, a precursor to NE, in combination with Atomoxetine(ATMX), an approved NE-reuptake inhibitor, to improve learning and memory in the Down syndrome mouse model.
The news release notes that "Further tests will be needed to determine whether formoterol might be an appropriate treatment for people with Down syndrome or whether to use another drug that activates the same receptors… The dose used in this study was many times higher than that used for asthma treatment, he cautioned, so it is not known whether it is safe. A lower dose might work, or other drugs that affect beta-2 adrenergic receptors might be safer and more effective in humans. Researchers also want to explore what parts of learning — taking in new information, remembering it or both — are affected by the drug treatment…"
Additional information on this research breakthrough may be found in the LA Times article.