(October 30, 2024) – Greenwood, SC – The Greenwood Genetic Center (GGC) is collaborating with Gene Spotlight, a nonprofit medical research and advocacy organization, to perform its first high-throughput drug screen for patients with a specific variant in the gene that causes Mucopolysaccharidosis, type 1 (MPS1) also known as Hurler syndrome, Scheie syndrome, or Hurler-Scheie syndrome.
MPS1 is a rare lysosomal storage disorder caused by the inability of the body’s cells to produce enough of an enzyme called alpha-iduronidase that breaks down harmful substances. The toxic buildup of these substances leads to symptoms including coarsening facial features, hearing loss, skeletal and spinal deformities, cardiac issues, and developmental delays.
GGC researchers will screen approximately 1,800 compounds, most of which already have FDA approval for other purposes, to determine if they increase the activity of the alpha-iduronidase enzyme in cells with an MPS1 variant.
“Through ongoing work to better understand how specific genetic changes cause MPS1, we created cell-based tools that will be used to screen a library of FDA-approved drugs for their ability to increase alpha-iduronidase enzyme activity,” said Rich Steet, PhD, Director of Research at GGC. “We are hopeful that of the compounds we screen, we will find a few hits to pursue further as a potential therapy.”
The team identifies a hit as a drug that improves enzyme activity by 25% or more.
“For many of these lysosomal storage disorders, we can see significant clinical improvements with even a small increase in enzyme activity,” added Steet. “If we can go from 1-2% activity to 10-15% activity, that could be life-changing for these patients and their families.”
The project is being funded by Gene Spotlight, a leading medical research non-profit organization committed to sparking breakthroughs in treatments and cures for rare genetic disorders, including lysosomal storage disorders and other rare diseases. Currently, 95% of rare diseases have no approved treatment.
“By screening so many compounds that already have FDA approval, we can potentially identify an effective treatment that we could pull off the shelf and administer immediately,” said Mike Lyons, MD, Curry Chair in Translational Genomics and Therapeutics at GGC. “We are excited for the potential that this and future drug screens can have to improve the quality of life for patients with rare diseases.”
Photo: Dr. Rich Steet loads plate of test compounds into instrument.