Dr. Barbara Bailus, Keck Graduate Institute (KGI) Assistant Professor of Genetics, recently received a distinguished New Investigator Grant from the Foundation for Angelman Syndrome Therapeutics (FAST) of $500,000 over a two-year period. This grant will support a research project titled, “Targeting Angelman Syndrome Therapeutics to the Brain Utilizing Novel Cell-Penetrating Peptides.”
The origins of this project can be traced back to her 2013 research which Dr. Bailus conducted as a PhD student in the lab of Dr. David Segal at UC Davis. In the lab, they designed an artificial transcription factor—a precision-tailored molecule designed to bind DNA and regulate transcription in a preprogrammed manner—to successfully treat Angelman syndrome (AS) in a mouse model.
Dr. Bailus’s research at UC Davis focused on directly treating AS by delivering purified artificial transcription factors to the brain via a peripheral injection, activating the silent copy of the missing or non-functional gene responsible for AS. The peptide allows one to inject the protein either subcutaneously—directly under the skin—or intraperitoneally—in the abdominal body cavity. In this manner, the therapeutic protein is able to cross the blood-brain barrier, entering the neurons of the brain, activating the silent gene of interest, UBE3A.
“Usually in these scenarios, you must directly inject the drug into the brain, or fluid surrounding the brain,” Dr. Bailus said. “The trick here was to find a way around that. We added a cell-penetrating peptide to the protein, which is essentially a backstage pass to the brain, carrying the protein across the blood-brain-barrier and into the neurons of the brain.”
Over the course of the two-year grant, Dr. Bailus plans to test up to three novel cell-penetrating peptides to carry the therapeutic targets into human cells and into the brain of Angelman syndrome mice.
“This is a very exciting project that could change the landscape of drug delivery for neurologic disorders. There are many companies and stakeholders that are very much looking forward to the results of this study,” said Dr. Allyson Berent, Chief Science Officer for FAST, “and we are thrilled that the disease model being utilized to test these novel constructs is Angelman syndrome.”