As many of you know, I love genetics. So when I was perusing Nature on my iPad this morning (working on my New Year's resolution), I went straight for the article with the word "allele" in the title. (An allele is a version of a gene; we all inherit two alleles of each gene -- one from our mother and one from our father. This concept is very important for the article I read.)
The article was about a drug that was found to "unsilence" an allele in mice, serving as treatment for a disease called Angelman syndrome, a severe neurodevelopmental disorder.
Normally, we have two potentially active alleles of each gene. However, in a particular gene called Ube3a, only the maternal allele "works" due to a process called imprinting. The paternal allele is effectively silenced. So if the maternal gene is mutated or dysfunctional in some way, then the gene product of Ube3a doesn't get made -- there is no functional paternal allele to take over. The result is Angelman syndrome, according to this article.
So researchers looked at 2,306 different molecules (yes, that number is right) to see whether any of them would "unsilence" the paternal allele. One -- an anticancer drug called a topoisomerase inhibitor -- did. The scientists eventually found another topoisomerase inhibitor that worked even better, and tested it in vitro (in culture) and in vivo (in living mice). In both cases, the Ube3a gene was activated in the target neurons.
While this type of treatment has a long way to go before it is approved for use in humans, this research study does offer hope to some people. (Angelman syndrome is estimated to affect 1 in 15,000 births, according to the Nature article.)
This article also contains many concepts that I learned in my genetics course. Which made it easier to understand, of course, and also reminded me that what we learned was significant and will be important in my future as a physician-scientist.
Background: image of a rat neuron.