Researchers from four organizations have identified more than 200 new proteins that bind to normal and mutant forms of the protein that causes Huntington's disease (HD).
HD is a fatal inherited disease that affects 30,000 Americans annually by laying waste to their nervous system. The research was led by Buck Institute faculty member Robert E. Hughes, PhD. Results of the study, which may facilitate the discovery of an effective treatment for HD, will be published in the May 11 edition of PLoS Genetics, an online, open-source journal, enabling scientists from around the world to take advantage of the findings immediately.
The work, which involved high-tech screening of the human genome and proteome, was unprecedented both in terms of its scale and in the way the protein interactions were validated in a genetic model of the disease. 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. This indicates that a significant number of the proteins might be potential drug targets for HD.
Now that researchers have discovered the interacting proteins using human libraries and human protein extracts and tested them in the fly, Hughes says the next step is to bring the research back into the mammalian world. The new genes and proteins discovered in this study are being screened and analyzed in cultured mammalian cells; the ones that show activity in ongoing experiments will be tested in mouse models of 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."