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Study Suggests Treatment for Down's Syndrome

Norepinephrine prodrug L-DOPS led to improved contextual learning in mouse model

FRIDAY, Nov. 20 (HealthDay News) -- Treatments that address deficient norepinephrine-mediated neurotransmission could treat cognitive dysfunction in Down's syndrome, according to the results of animal research published in the Nov. 18 issue of Science Translational Medicine.

Ahmad Salehi, M.D., of the Stanford University Medical School in California, and colleagues analyzed data from the Ts65Dn mouse model of Down's syndrome. These mice showed normal cued learning, which is also relatively intact in humans, but had a notable deficiency in contextual learning. The mice also showed fewer neurons in the locus coeruleus.

The researchers found that treating mice with the norepinephrine prodrug L-DOPS led to markedly increased hippocampal norepinephrine levels. Treatment in Ts65Dn mice significantly improved their contextual learning, and was associated with increased freezing and improved nesting behavior. After treatment ended, the mice's poor nesting behavior resumed.

"Our findings suggest that enhancing norepinephrine neurotransmission may be useful in treating cognitive disability in Down's syndrome. An important question is which age group to target. The murine studies reported herein suggest that young adults with Down's syndrome, in whom pathology is present but not advanced, may be appropriate," the authors write. "If the status of locus coeruleus neurons and their targets in mice mirrors those in humans, at this stage of the disorder post-synaptic adrenergic receptors will be present and responsive to pharmacologically induced increases in brain norepinephrine levels."

The authors reported that a patent application related to this work has been submitted. Chelsea Therapeutics provided L-DOPS for the study.

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