RP-115: A Novel Biomarker of Astrocyte Dysfunction and Glutamate Dysregulation in Brain and Spinal Cord in ALS
Abstract
Amyotrophic lateral sclerosis (ALS, Lou Gehrig s disease or more often referred to in some countries as Motor Neuron Disease) is a progressive, degenerative neurological condition that affects the limbs and the muscles that control breathing and swallowing. In some individuals, other parts of the brain are also affected leading to a form of dementia. ALS involves selective degeneration of nerve cells that control movement. One pathway to cell death in ALS is excessive stimulation of motor neurons, or excitotoxicity. The major excitatory transmitter in the nervous system is called glutamate and glutamate levels are controlled by a transporter protein called EAAT2. There is currently no type of scan that detect these specific biochemical changes. This is a limitation not only for the diagnosis of ALS but also for the development of new treatments. Rio Pharmaceuticals have discovered a molecule called RP-115 which can be turned into a dye to show the levels of EAAT2 in the nervous system. This project will test whether RP-115 can be used as a marker of critical changes to cells in the brain and spinal cord in ALS. The project will implement and test the utility of RP-115 imaging with PET as a disease biomarker in ALS. Ultimately, this project will accelerate the development of transformative new therapies for ALS. It will develop a new specific imaging biomarker that can be used to select the most promising candidates for full-scale trials. All types of patient with ALS are potential beneficiaries of a more rapid and efficient pipeline for therapeutic discovery. By providing an objective marker of disease RP-115 will reduce disparities in access to trials, thereby benefiting minority groups. An imaging biomarker is particularly well-placed to help patients with early memory and cognitive symptoms by providing objective insight into the pattern of damage in the brain. The potential clinical applications also include diagnosis, with the benefit of enhanced diagnostic certainty in some subtypes of ALS. There are no major risks. The current project will take 2 years to establish the utility of this biomarker for use in patients with ALS, producing evidence of safety and acceptability, preliminary data to design larger studies and trials and an emerging trans-Pacific network to support those trials. Emergence of a new therapy, first tested with RP-115, is expected within 5 years of beginning this program. Eradication of death and suffering from ALS requires transformative new therapies. The contribution of this project will be to drive the selection of the most promising candidates, reducing the number of failed trials, and potentially reducing the time to transformative therapies by many years.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310465
Entities
People
- Michael Osullivan
Organizations
- United States Army
- University of Queensland