ATLANTA–Two Georgia State University chemists have created new medicinal molecules that may help cure genetic diseases such as acute myeloid leukemia (AML) and amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease.
David Wilson and David W. Boykin, both Regents’ Professors of Chemistry, have been working together for 30 years to develop compounds that could affect DNA and RNA and keep genetic mutations from causing disease.
AML, a blood cancer, begins in the stem cells inside bone marrow where blood cells are made. A genetic mutation in AML patients makes their bone marrow go haywire. The affected marrow cranks out cells that are similar to white blood cells but have no ability to fight infection. So many of these leukemic cells are produced they crowd out normal white blood cells, leaving patients prone to infection, and red blood cells, leaving patients anemic.
AML kills 65 percent of patients under 60 years of age, and about 90 percent of patients older than that.
Wilson and Boykin, in collaboration with associate professor Gregory Poon, learned in earlier studies that the problem was a transcription factor called PU.1. Transcription factors are proteins that tell DNA when to start and stop making RNA, which makes new cells.
The research group developed a compound that binds to the DNA in a bone marrow cell. That compound blocked PU.1 from also binding to the DNA. As a result, the sick bone marrow cells stopped pumping out leukemic blood cells.
“If a transcription factor gets disturbed, it might cause a gene to turn on without control, and that’s when you get something like acute myeloid leukemia,” Wilson said.
The new inhibitor has not been tested in patients yet, but Dr. Ulrich Steidl at the Albert Einstein School of Medicine has produced excellent results in mice and in sample cells from human patients.
In collaboration with a group from University College London, researchers have developed a different compound that has shown promising results against ALS. In that disease, large, malformed RNA molecules suck up all of the raw materials that normal RNA would use to build healthy proteins. In that disease, the Georgia State drug binds to the malformed RNA molecules, preventing them from binding to and using up those raw materials.
Wilson and Boykin’s research has been supported by grants from the National Institutes of Health and The Leukemia and Lymphoma Society.
W. David Wilson
David Wilson’s research is focused on nucleic acid structure and the interactions of nucleic acids with molecules that range from small synthetic compounds to large proteins, such as transcription factors, that are the proteins responsible for orchestrated, temporal expression of specific genes.