Advancing drugs for neurodegenerative conditions
Investigating how genes are activated, Prof. Rivka Dikstein is examining a protein complex called Spt4/Spt5. This complex is involved in the transcription of genes that, in their underlying sequence, are characterized by lengthy stretches of repeated patterns—a hallmark of neurodegenerative conditions including Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Because the activation of Spt4/Spt5’s transcription-promoting activity depends on an enzyme called Pol II, Prof. Dikstein theorized that Spt4/Spt5-Pol II binding could serve as a target for a drug-based intervention. Working together with Staff Scientist Anat Bahat, Prof. Dikstein has positively identified some 150 that inhibit Spt4/Spt5-Pol II binding. As very few of the compounds identified in this screening process are found in the library of FDA-approved medicines, Prof. Dikstein’s approach is revealing new, under-explored avenues of drug discovery.