The discovery of a new class of molecules holds promise for blocking the clumps of protein that clog the brain in Alzheimer’s disease. This discovery was made possible by the NIH Roadmap Molecular Libraries Initiative. This initiative uses high tech robots and molecular genetics to speedily screen molecules for their biological effects.
To do that amount of screening by hand would take a person eight hours a day, five days a week for 12 years to do what can now be done in three days, explained Dr. Chris Austin, Director of the NIH Chemical Genomics Center (NCGC).
At the NCGC labs in Rockville Maryland, the robots work day and night performing automated high throughput screening. This technique borrowed from industry can rapidly screen vast libraries of chemicals, genes, or drugs for their effect on cells and proteins. The Center transforms the findings into probes for use by NIH scientists in search of better treatments for disease.
The NCGC in their largest search to date have provided small molecules screening in Alzheimer’s disease. Researchers studying Alzheimer’s disease at the University of Pennsylvania are using Genomic Center probes to pinpoint ATPZs that block the tau protein clumping. The researchers are following up with studies of ATPZs in transgenic mice in hopes of paving the way for a new class of drugs to treat Alzheimer’s.
At Vanderbilt University, Roadmap grantees have used high throughput screening to pinpoint two compounds that selectively tweak a subtype of receptor, call M1 for the brain messenger chemical acetylcholine which is known to be critical for learning and memory. This information will help develop a strategy for treating thinking deficits in schizophrenia and Alzheimer’s disease
At Scripps Research Institute’s Comprehensive Center for Chemical Probe Discover and Optimization, researchers have developed high throughput technology for quickly screening tens of thousands of compounds and the researchers are unraveling the workings of still uncharacterized enzymes which previously was a labor intensive task. This has helped the researchers discover compounds that can block certain cancer related enzymes.
Another Roadmap center grantee along with colleagues at the University of New Mexico’s Center for Molecular Discovery, have developed a high throughput way to simultaneously sort out complex cell mixtures and molecular interactions. By doing this, they discovered a new compound called G-15 that regulates cell responses to estrogen. The research will advance the understanding of estrogen’s role in breast, uterine, endometrial, and ovarian cancers. Their findings may also find applications in other estrogen related disorders such as immune system disorders and multiple sclerosis.