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Researchers identify drug candidate for Angelman syndrome

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Jessica Wright
17 November 2011

Dark disease: Mouse brains expressing a fluorescent version of UBE3A (top) don’t show any fluorescence when the maternal copy of the gene is missing (above).

Researchers have identified a compound that shows promise as a treatment for Angelman syndrome, a developmental disorder related to autism. The unpublished results were presented Tuesday at the 2011 Society for Neuroscience annual meeting in Washington, D.C.

Using a fluorescent version of the Angelman syndrome gene, the researchers screened thousands of compounds to identify a small molecule that can treat the disorder. Because the details are unpublished, the researchers declined to name the molecule, but the report was received with enthusiasm nonetheless.

“This is very, very exciting,” says Emanuel DiCicco-Bloom, professor of neuroscience at Rutgers University in New Jersey, who was not involved with the work. “It’s a beautiful assay and pretty unique.”

Angelman syndrome is caused by the loss or inactivation of the UBE3A gene, which codes for a protein that regulates the levels of other molecules. UBE3A is one of a subset of genes that undergoes imprinting, meaning that only one copy of the gene, in this case the maternal copy, is active.

This makes Angelman syndrome a very promising disorder for which to find a therapeutic, says Ben Philpot, associate professor of cell and molecular physiology and the University of North Carolina, Chapel Hill. “[Our] strategy is to try to identify a small molecule compound that can awaken the dormant allele.”

Follow the light:

The strategy relies on a mouse engineered to express a fluorescent version of the UBE3A protein1. The brains of these mice light up, but not when the maternal copy of UBE3A is deleted.

The researchers bathed the neurons from these mice in a series of more than 2,000 compounds, looking for one that would activate paternally expressed UBE3A. They found one that rescues fluorescence when used at low concentrations.

The compound also has long-term effects in mice. When injected into mouse spinal cords, it turns on expression of paternal UBE3A in these cells. Mice injected with the molecule once a day for two weeks continue to express the paternal allele for up to three months, the study found.

The researchers are also seeing promising results in mouse brains, Philpot says.

Still, although the compound shows great potential as a treatment for autism, there is need for caution, researchers say.

“I would want to know whether it turns on the expression of other imprinted genes,” says DiCicco-Bloom, who mentions a family of genes that are important in development and are paternally imprinted. “I wouldn’t want a reagent that interfered with those kinds of imprinting genes.”

Preliminary experiments have shown that the compound is very specific, Philpot says, but he also advocates the need for caution.

“This isn’t a treatment for Angelman syndrome yet,” Philpot says. “It still needs to be vetted through the proper clinical and preclinical protocols.”

For more reports from the 2011 Society for Neuroscience annual meeting, please click here.


1: Dindot S.V. et al. Hum. Mol. Genet. 17, 111-118 (2008) PubMed


Name: Jennifer Johnson
18 November 2011 - 2:28AM

This is very exciting work. Thank you for the report. Please continue to keep us informed of future developments out of this lab.

Name: Linda Hammill
21 November 2011 - 1:36AM

Indeed, this is very exciting work being done. My son was diagnosed with Angelman Syndrome in 1989. Throughout the years, I found the scientifics and research unfold, but today the researchers are even more incredible! God Bless Them. The UBE3A gene is quite amazing in that it not only involves A/S, but also Autism, the E6-AP (of UBE3A)involves cancer(s) and that as people age, there is less and less UBE3A cells, which may help those with Alzheimers. Thank you so very much and wishing you success in all your endeavors.

Name: SJ
21 November 2011 - 2:32AM


Name: Anonymous
21 November 2011 - 1:04PM

With a child just diagnosed, this gives me great hope. Please keep up the good fight and know a lot of people are counting on you. Thank you! Hope is what is helping me get through the day right now.

Name: courtney harpur
16 March 2012 - 11:51PM

I think that ,if the drug has been used in the treatment of anything else, such as cancer,then the answers are out there already.Its very likely that angelmans sufferers would have been treated & therefore would show the effect, not least of all if the paternal gene was activated. A blood test would show this. The data base is there & probably so are the answers. Think about this--MAYBE, JUST MAYBE, an Angelman kid has been treated for cancer,and maybe just happened to start talking again! What do you think? My email is- charpur@orcon.net.nz

Name: lil k
19 February 2013 - 9:28PM

keep a good fight trying to come up with a cure for the Angleman Syndrome

Name: saritha
22 July 2013 - 6:24AM

thanks a lot for taking angels. we r eagerly waiting for that day when angels will be free from their problem

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