CRISPR research tackles rare genetic disorder in children
Michigan State University scientists will use the latest CRISPR technology to study two extremely rare genetic mutations that leave children severely disabled with seizures and involuntary movements.
CRISPR, or clustered regularly interspaced short palindromic repeats, is a gene-editing technology that is now playing a major role in drug discovery.
With the help of a $48,000 starter grant from the Bow Foundation, Rick Neubig, chair of the Department of Pharmacology and Toxicology, will test existing drugs and identify possible new treatment options to help the roughly 60-known cases in children worldwide that are affected by GNAO1 disorders.
GNAO1, or G Protein Subunit Alpha O1, is a gene that is expressed at high levels in the brain and its mutations can trigger seizures and uncontrollable muscles movements in children as early as a few days old.
While there are only a few documented cases, Neubig indicated there may be many more children with the disorder that physicians don’t even know about yet.
“The number of kids identified with GNAO1 mutations is increasing rapidly, and it’s possible numbers are now getting into the hundreds,” Neubig said.
The disorder has left scientists and families searching for answers and looking for treatments.
Two different kinds of genetic mutations, described by the Neubig lab last year, are the culprits in conditions of Early Infantile Epileptiform Encephalopathy and Neurodevelopmental Disorder with Involuntary Movements.
“We’ve picked the two mutations that are more common among those reported,” Neubig said. “Obviously common is relative, though, when you talk about rare diseases. In this case, we’re talking five to 10 kids with these specific mutations.”
Over a period of 12 months, Neubig and his team will develop mice that will carry each of the mutations. During this time, they will analyze how these rogue genes change the mouse brain and begin preclinical therapeutic trials using existing drugs that can control the neurodevelopmental symptoms that occur in human patients. Using existing drugs can often help speed up FDA approval on new therapies.
“Dr. Neubig’s research gives the promise of hope to the dozens of GNAO1 patients around the world,” said Emily Bell, one of the founders of the Bow Foundation. “By helping the medical community better understand the impact of these disorders, it could also open doors to better treatment options for patients.”
Bell’s co-chair agreed.
“We’re excited to fund this new research project and are thrilled to be working with MSU,” said Alice Fox. "We look forward to gaining new insights and funding additional studies as we work to increase GNAO1 awareness and change lives.”