Researchers in Cleveland and London, funded by the National MS Society have achieved a new way to visualize and monitor the loss and repair of nerve-insulating myelin over time, creating a non-invasive tool to identify compounds with future potential to treat MS. Their studies used PET (positron emission tomography) imaging in rats as a non-invasive way to detect myelin damage and its subsequent repair by an experimental compound. Yanming Wang, PhD, Chunying Wu, PhD, Robert Miller, PhD, and colleagues at Case Western Reserve University and Imperial College, London, recently reported results in the Annals of Neurology
In multiple sclerosis, myelin, the fatty substance that surrounds and protects nerve fibers, is attacked and destroyed, leading to many possible neurological symptoms. Several therapies currently under development aim at promoting myelin repair, but there is no established means of observing myelin repair over time in a non-invasive manner. MRI scans are commonly used to image disease activity in the brain, but MRI is not sensitive enough to reveal specific information about myelin damage or repair. Thus, a new imaging technique is crucial for assessing how well new therapies aimed at myelin repair work.
With funding from the National MS Society, the U.S. Department of Defense, and the National Institutes of Health, Dr. Wang and colleagues have developed and tested a new molecular probe called MeDAS that, when injected into the bloodstream, enters the brain and spinal cord and binds specifically to myelin. After injecting rats with a trace amount of MeDAS that is tagged with a radioactive tracer, they then imaged the spinal cord using PET (positron emission tomography), which traced the radioactivity to create images that visualize where in the spinal cord the MeDAS went.
They observed that MeDAS labeled only regions with intact myelin, and not regions where myelin is damaged or destroyed. Thus, MeDAS is a “myelin-specific label.” Next, they used two models for MS in rats, including EAE, to validate this new technique. Subsequent imaging studies showed a strong correlation of MeDAS uptake with myelin content, enabling PET imaging to identify regions in which myelin had been lost compared to regions in which myelin remained intact.
Finally, in rats treated with an experimental therapy previously shown to stimulate myelin repair in the laboratory, the team was able to use MeDAS-PET imaging technique to monitor the effectiveness of myelin repair in the spinal cord. Importantly, they also showed that MeDAS-PET imaging could detect and quantify the amount of myelin independent of inflammation present in the brain. This is important because inflammation is present in the brains of people with MS.
This novel study was performed in rats, and much work, including safety studies, will be needed before imaging with MeDAS can be done in humans. In the meantime, this technique may be useful for screening the potential of various therapeutics currently under development for repairing myelin. Ultimately, it is possible this technique could be used to evaluate results of clinical trials focusing on repairing the brain and spinal cord in order to restore function in people with MS.
about research to repair tissue damage in MS.