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Study in mice yields Angelman advance
Date:2/13/2013

e, the compound made obtaining LTP significantly easier, although observing LTP in Angelman mice is still more difficult than in normal mice, Marshall said.

Paths to a therapy

Although the bottom line of the study is that the scientists now have taken a step toward understanding what seems to be going wrong in Angelman syndrome, the path toward a therapy for people is not so simple, Marshall said. For one thing, the team hasn't yet shown that mice benefit cognitively or behaviorally from CN2097's ability to protect PSD-95 from Arc and therefore to restore BDNF signaling and synapse formation.

"Can we actually rescue learning deficits?" Marshall said. "That would be the next stage to test. We haven't gotten that far yet."

Also, CN2097 breaks down in a matter of hours, so it may have to be administered quite frequently to sustain its beneficial effects.

But the research is extremely encouraging, Marshall said, because it pinpoints a potentially successful therapeutic strategy. Now scientists have two promising options. One is simply to keep testing CN2097 to determine whether it benefits live, behaving mice and what the best dosing regimen would be. The other is for scientists to take all that they have learned over the course of their experiments and use that knowledge to identify other compounds that might work like CN2097, but do so for longer periods of time.

"We think we are on the right track," Marshall said. "The goal is to try to help these kids. We want to do that as rapidly as possible."

Marshall has launched a new start-up company, Angelus Therapeutics, in hopes of raising the money required to perform more preclinical studies in animals. Further tests of the compound are necessary to lay the groundwork for possible future clinical trials.

Farther into the future, he added, the team can also look at other brain disorders that might also have to do with BDNF, synapse formation, le
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Contact: David Orenstein
david_orenstein@brown.edu
401-863-1862
Brown University
Source:Eurekalert  

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