Multiple Sclerosis (MS) is a disease that results in damage to the brain, spinal cord, and optic nerves, collectively termed the central nervous system (CNS). Signals travel through the CNS via neurons, which are insulated with a fatty substance called myelin. The signals in neurons with myelin insulation can travel up to 300x faster than the signals in unmyelinated neurons. Patients with MS experience a loss of CNS myelin, which results in decreased nerve impulse speed and damage to the underlying neurons. This damage leads to symptoms of MS that vary in type and severity, but may include gait impairments, numbness and tingling sensations, double vision, and bowel and bladder issues. Furthermore, because MS impacts the brain, approximately half of all MS patients experience impairments in cognitive function.
The focus of this research project is to find a treatment for learning and memory problems caused by MS, for which there is no FDA-approved treatment. Our approach began with a human study, in which we examined the brains of patients with MS using an MRI scanner. We then correlated the measured levels of a neuropeptide of interest, N-acetylaspartyl glutamate (NAAG), to how the patients performed on a battery of cognitive tests. We discovered that the higher the levels of brain NAAG, the better that patient performed on the cognitive tests. In a subsequent collaboration with the Johns Hopkins Brain Science Institute, we found that daily administration of a chemical compound that upregulates the concentration of brain NAAG caused an improvement in cognitive function by over 100% in an animal model of MS. We are currently evaluating the optimal dose of this chemical compound and it’s exact mechanism of action, and we hope that a compound will be available to test in MS patients in the near future.
Dr. Kristen Rahn is an Instructor in the Departments of Psychiatry and Neurology at Johns Hopkins. She completed her postdoctoral training at Johns Hopkins under the guidance of Dr. Adam Kaplin, and joined the faculty in 2012. Her research interests include Multiple Sclerosis, Transverse Myelitis, and depression.
Read “Cognitive Impairment in Multiple Sclerosis: A Forgotten Disability Remembered” | A Dana Foundation Article