The Huntington’s disease (HD) study involved high-tech screening of the human genome and proteome, and was unprecedented both in terms of its scale and in the way the protein interactions were validated in a genetic model of the disease, the researchers said.
In addition, by conducting additional experiments in fruit flies genetically altered to express features of human HD, scientists showed that changing the expression of these interacting proteins affected the degree of damage seen in the fly neurons. The Buck Institute said that this indicates that a significant number of the proteins might be potential drug targets for HD.
The research was led by Buck Institute faculty member Robert Hughes. He said that now researchers have discovered the interacting proteins using human libraries and human protein extracts and tested them in the fly, the next step is to bring the research back into the mammalian world.
The new genes and proteins discovered in the study are now being screened and analyzed in cultured mammalian cells and those that show activity in ongoing experiments will be tested in mouse models of HD.
The research, which will be published in the May 11, 2007 edition of PLoS Genetics, has been supported by HD advocacy organizations. It is hoped that making the results public will enable scientists from around the world to take advantage of the findings immediately, possibly facilitating the discovery of an effective treatment for HD.
“Here at the Buck Institute, we’re going to be focusing on a few dozen proteins,” said Hughes. “Effective follow-up on any target protein depends, in large part, on how much expertise a scientist has with that target. We are hoping that researchers will look at this study and that those with specific expertise in a particular protein will move forward with their own inquiries.”