New Imaging Platform for MS Preclinical Trials
Cedars-Sinai and NIH Imaging Experts Develop the First Proven Technique for Noninvasive Tracking of Brain Lesion Self-Repair
Investigators at Cedars-Sinai and the National Institute of Neurological Disorders and Stroke have pioneered a way to monitor the self-repair of brain lesions in a nonhuman primate model of multiple sclerosis (MS). Their study, published in the peer-reviewed journal eLife, used highly sensitive 7-Tesla MRI to track the progress of brain lesion self-repair.
“This is the first proven noninvasive imaging approach for capturing this process of self-repair in the living brain,” said Pascal Sati, PhD, director of the Neuroimaging Program in the Department of Neurology at Cedars-Sinai and co-senior author of the study. “This MRI approach provides an important new tool to test the effectiveness of therapies aimed at promoting remyelination in the central nervous system.”
Multiple sclerosis is a disease of the brain and spinal cord in which the body’s immune system attacks a sheath called myelin that protects nerve fibers. The process, called demyelination, creates lesions that disrupt the brain’s communication with the body and cause symptoms that include pain, fatigue, and loss of vision and coordination. The body sometimes repairs the myelin sheath on its own, a process called remyelination.
“MS affects millions of people worldwide, and remyelination of MS lesions is an important therapeutic target because it restores nerve conduction and prevents loss of nerve cell function,” said Nancy L. Sicotte, MD, chair of the Department of Neurology and director of the Multiple Sclerosis and Neuroimmunology Program at Cedars-Sinai.
Sati and fellow investigators studied common marmosets that had a disease called experimental autoimmune encephalitis, which closely resembles MS and causes inflammatory demyelinated lesions in the brain. The researchers performed highly sensitive MRI imaging of the animals’ brains biweekly and tracked the formation and self-repair of their lesions.
“We used serial in vivo MRI to identify lesions that had repaired themselves as well as those that were chronically demyelinated and would not heal,” Sati said. “We then compared our imaging results to samples of the actual brain tissue that included the same lesions.”
The MRI was 100% sensitive and 90% specific in identifying the brain lesions that had self-repaired.
“Because we imaged so frequently, we were able to track the formation of a lesion, then see the lesion begin to repair itself and, finally, see it return to almost a normal pre-lesion level that indicates the tissue was able to spontaneously repair itself,” Sati said. “The tissue samples analyzed by histopathology confirmed that the in vivo MRI was able to capture that with high accuracy.”
Sati and fellow investigators envision this nonhuman primate model of MS as a bridge between preclinical studies conducted in rodents, which do not form brain lesions that replicate MS, and clinical trials in humans.
“Investigators testing a very promising remyelinating therapy could use this animal imaging platform to further validate their initial finding in rodent models before committing to the time and expense of conducting a human trial,” Sati said.
Sati said that the 7-Tesla preclinical MRI scanners used in the study, which are specifically designed for use in animals, are prevalent at academic research centers, and that the MRI sequences the investigators employed to identify remyelination have long been in clinical use.
Although the imaging done in this study isn’t practical for use in humans due to the expense involved in conducting biweekly brain scans and the limited availability of 7-Tesla clinical MRI scanners for humans, Sati said there is a possibility of adapting the test for use in 3-Tesla scanners commonly found in hospital imaging departments.
According to Sati, the next step in this work is to use this animal imaging platform to conduct tests of an actual therapy promoting remyelination in nonhuman primates.
Funding: This study was funded by the National Institute of Neurological Disorders and Stroke Intramural Research Program and through a Cooperative Research and Development Agreement with Vertex Pharmaceuticals.
Read more in Discoveries: No Time for MS