Daniel Reich at the National Institutes of Health, Calabresi and colleagues showed that other novel imaging technologies – such as diffusion tensor imaging (DTI), which measures the flow of water particles in tissue, and magnetization transfer, which measures the transfer of energy particles – could specifically detect myelin and nerve fiber damage and track them over time. Drs. Sharmilee Gnanapavan at Queen Mary University and Giovannoni searched for biomarkers that would indicate tissue damage or repair via a blood or spinal fluid sample. This research has indicated several possibilities, including neurofilament, a threadlike molecule found in nerve cells that can be measured in spinal fluid. Neurofilament levels may be a good indication of whether nerve cells are being damaged and whether disease is progressing. If validated in further research, measuring neurofilament may prove to be a quick measure of whether potentially neuroprotective drugs are working, enabling faster clinical trials. Drs. Aaron Field, Andrew Alexander at the University of Wisconsin-Madison and colleagues reported on an effort to combine DTI and diffusion spectrum imaging, which enabled them to examine nerve fibers that intersect each other. The team has been able to minimize the imaging time necessary for this hybrid approach and increase its accuracy. Scientists also reported progress in using clinical tests that can assess symptoms simply, but may correlate with underlying disease activity. Drs. Kathleen M. Zackowski, Calabresi and colleagues showed that “sensorimotor” dysfunction that was picked up by testing vibration sensation and ankle strength correlated with disease activity on advanced MRI technology. Also, Dr. Balcer’s research indicates that tests of visual acuity – perception of light gray letters of progressively smaller size on a white background – correlate with OCT and other imaging results. Goal 3: Design human clinical trials of repair and protection therapies. The ultimate goal of this initiative was to lay the groundwork for clinical trials of strategies to protect and repair the nervous system.
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MSConnection • SPRING 2011
In brief: • Clinical trials are underway to evaluate experimental strategies for nervous system protection and repair. • New clinical trial designs and outcome measures are in development to speed up the testing of promising agents. • Collaborations are expediting and enhancing the quality of clinical research. Here is a sampling of studies that are underway or planned in collaboration with team members of this initiative: • Dr. Rowitch is conducting an industry-backed Phase I study to study the safety of neural stem cell transplantation in children born with a lack of myelin; this small, early study would also serve as a “proof of principal” for this strategy. • Dr. Raj Kapoor with London’s National Hospital for Neurology and Neurosurgery is launching a Phase II study of phenyltoin to determine its effects on neuroprotection in optic neuritis, funded by the National MS Society and the MS Society of Great Britain and Northern Ireland; the study design takes lessons learned from a failed study of lamotrigine in SP MS. Both these drugs are sodium channel blockers, drugs that enable tiny pores along nerve fibers to improve nerve impulse conduction. The value of collaboration Team leaders unanimously agreed that this collaboration has moved the field of repair in MS forward exponentially. Dr. Coetzee noted that the Society is evaluating program outcomes to determine how to sustain the momentum created by these teams: “We are going to continue to move our work forward and share it worldwide to continue to speed research to repair the nervous system in MS. The dream is stopping MS in its tracks and of restoring function that has been lost. This is topmost in the hearts and minds of people who have MS, as well as their loved ones.”