http://www.nationalmssociety.org/Highlights-ReplacingCells.asp

Replacing Cells Lost in MS

One of the most exciting areas of MS research is the effort to transplant myelin-making cells into the central nervous system. These cells may be able to repair damage to myelin, regenerate injured axons and restore nerve signal conduction. Jeffery Kocsis, PhD (Yale University, New Haven, CT) is funded by the Society* to explore the possibilities of cell transplantation in rats, and he discussed this research at “Neuronal Injury in MS and Related Disorders: Mechanisms and Prevention,” a Society-funded workshop held in New Orleans in March 2001. Thanks in part to his findings, this research will soon enter early clinical trials in people with MS.

“Therapies that regulate the immune attack on the central nervous system in MS will continue to develop,” said Kocsis. “But other approaches may be necessary to improve nerve conduction in brain tissue where myelin and axons have already been damaged.”

The key to cell replacement therapies is finding the right cells – not an easy task. “This is a major effort right now, with researchers investigating a variety of cell types,” said Kocsis. “First, we need to show that the cell can survive – transplanting any organ or cell carries the risk of rejection, in which the immune system attacks the new tissue. We also need to make sure that the cell will develop without abnormalities. Finally, we need to determine if the cell can migrate to areas of myelin damage and form new tissue.”

One promising prospect is Schwann cells, myelin-making cells from the peripheral nervous system (the network of nerves outside the brain and spinal cord), about which Kocsis published findings in the February 1, 2001 issue of The Journal of Neuroscience. “We took Schwann cells from adult human nerves, froze them, and stored them for weeks to months,” he said. “The frozen cells were then injected into lesions in the spinal cords of rats.

“We found that the human Schwann cells formed relatively extensive myelin and that previously obstructed nerve impulse conduction improved. This was an important preclinical study, because it showed that Schwann cells from relatively older humans could migrate to areas of myelin damage and form working myelin.”

Based on this research, Kocsis’s Yale colleague Timothy Vollmer, MD, is planning a small trial of Schwann cell transplantation in 5 people with secondary-progressive MS. Kocsis’s laboratory will provide technical support, and has developed highly efficient ways of harvesting these cells from individuals who enroll in the study. Schwann cells will be taken from nerves in the participants’ feet, and transplanted into areas of myelin damage in the brain.

“This trial is being designed to determine if these cells can survive, and to make sure treatment is safe,” noted Kocsis. “We will attempt the procedure in one person at a time, and if there are any problems, we will stop the study. It is important to understand that we are not yet evaluating the effectiveness of this therapy.” If safety and tolerability of this invasive procedure can be shown, clinical trials to test its effectiveness will be planned which involve larger numbers of people and a well-controlled design.

Enrollment information for the initial study is available at http://www.nationalmssociety.org/Research-trialsrecruiting.asp, or via email, at msresearch@yale.edu.

Olfactory Cells

Kocsis is investigating another cell type that might be useful in replacement therapies – olfactory ensheathing cells (OECs) – in collaboration with Alexion Pharmaceuticals, Inc. (Cheshire, CT). OECs form the myelin sheath on nerve fibers in the nose.

“OECs have unique properties that make them good candidates for transplant,” said Kocsis. “They can replicate themselves and can grow into other types of nerve cells. Also, we are taking these cells from the snouts of pigs that are genetically programmed to inhibit immune-system rejection. They may prove to be a rich source for cell therapies.”

Kocsis’s team found that these OECs retain their potential to repair myelin after transplantation into rats (Nature Biotechnology, September 2000). “Using advanced techniques to record nerve conduction, we found that transplanting OECs improved the speed and distance of nerve conduction,” said Kocsis. “Our findings are important prerequisites for considering therapy in humans.”

The promise of cell-based therapies is evident, but Kocsis emphasizes the need to proceed carefully. “The ultimate goal is to find safe cells that can be used for safe transplantation.”

*funded in part through gifts from the NMSS Western Connecticut Chapter and the Dan Family through the NMSS Greater Illinois Chapter.