Development of Small-Molecule LDN/OSU-215111 for Gulf War Illness
Abstract
This research focuses on a novel series of small-molecules that has been proven capable of providing significant benefits in an animal model of Gulf War illness (GWI), which meets the challenge "revolutionize treatment and minimize negative side effects." Central nervous system impairments are the most ubiquitous among the various symptoms of GWI. Currently, there is no effective therapy to treat these neurological problems in GWI individuals. We and others have found that dysregulation of glutamate, the major neurotransmitter in the brain, may contribute to these deficits. Our laboratories have developed a series of novel small molecules that have been proven capable of normalizing dysregulation of glutamate in the brain. We have investigated one of our small-molecules in a mouse model of GWI. We found that this small molecule can prevent cognitive difficulties and mood deficits if the treatment starts earlier. Importantly, we also found that this small molecule can significantly ameliorate cognitive and mood problems when the symptoms are already present. These results indicate that this small molecule series has the potential to reduce several GWI symptoms and maximize quality of life. We have recently selected the best small molecule to progress to preclinical development. We expect to file an Investigational New Drug application with the U.S. Food and Drug Administration by July 2021 and hope to complete first-in-human clinical studies in healthy subjects by the end of 2022. In the present application, we will evaluate this best small molecule in two animal models in order to further validate the benefits. Should this small molecule pass all criteria for the Qualification Phase, we will move onto the Verification Phase in Gulf War Veterans, hopefully by September of 2023.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010828
Entities
People
- Chien-liang Lin
Organizations
- Ohio State University
- United States Army