Trial Results Move Miami Toward Vision

Posted by Sam Maddox in Research News on April 03, 2017 # Research

None of the six spinal cord injured subjects showed recovery (and they were not expected to) so the ground didn’t shake when the Miami Project announced that its Schwann cell clinical trial had completed its first phase.

So it’s not big news but it’s good news. The trial basically demonstrated that highly purified Schwann cells are safe and that patient recruitment, cell preparation and timing can be worked out. This sets the stage for more cell transplantation studies, including one enrolling now with chronic SCI patients (at least a year post-injury), combining Schwann cells with fitness training and rehabilitation.

The Miami Project trial also validated a scientist’s vision, formulated more than 40 years ago. In 1975, Richard Bunge, then at Columbia University College of Physicians and Surgeons, had the idea that a person’s own cells could be used to address spinal cord injury. He and his team, including his wife, Mary, also a neuroscientist and collaborator, and long-time colleague Patrick Wood, moved on to Washington University, where they figured out how to culture Schwann cells and apply them in many animal experiments. This progress kept them on track toward hoped-for clinical application. In 1989, Richard Bunge took the position as scientific director for the Miami Project; his wife and Pat Wood also joined the Project.

Richard Bunge died in 1996. But Mary Bunge and Wood remained in Miami, focused on Schwann cell transplant development; both are key members of the Miami Project team that completed the new study, “Safety of Autologous Human Schwann Cell Transplantation in Subacute Thoracic Spinal Cord Injury,” published in the Journal of Neurotrauma. Lead author is Kim Anderson; Principal Investigators are Allan Levi and James Guest (who is also a PI for the Reeve-sponsored North American Clinical Trials Network study of the drug riluzole).

This was a sub-acute trial; patients got cell transplants within four to seven weeks post injury. The transplanted cells were their own (autologous), harvested from a 15 cm segment of sural nerve (in the leg). This is a peripheral nerve, of course, which means it contains Schwann cells. These are the cells that make regeneration of peripheral nerves possible. They don’t exist in the central nervous system (brain or spinal cord).

The cells obtained from the leg nerve are cultured and purified, then injected into the cord. Each patient, days earlier, had laminectomy surgery to stabilize the spinal column. Surgeons reopened that incision to have direct access to the spinal cord for injection, using a syringe device developed by Geron for its stem cell trials, (discontinued in 2011). Two patients got five million cells, two got 10 million and two others got 15 million cells.

So the idea, imagined by the Bunge lab at Washington University in the 1970s, was to put Schwann cells into the damaged spinal cord to see if they might initiate repair and recovery as in the peripheral system.

I spoke with Mary Bunge, the materfamilias of Schwann cell science, about the new publication, and about the long road from lab to clinic. (Bunge is a former member of the Reeve International Research Consortium on Spinal Cord Injury). Mary, who turns 86 in early April, still goes to work almost every day. But she has announced her retirement: December 31, 2017 at midnight.

“This truly is a bench to bedside story,” Bunge said. “My husband had the vision that we could obtain peripheral nerve Schwann cells, purify them in culture, and use them to repair the central nervous system. There was a great deal of basic research to do but it was always in the back of our mind to use the knowledge we gained to help in the clinical setting.”

Bunge said the move to Miami was propitious: “A project of this scale really requires a village. The Miami Project provided that village.”

The first Schwann cell trial is a “building block,” Bunge said. “It’s a start. My work for the past 25 years has been looking at combination strategies. Schwann cells are a good beginning but because of the complexity of changes to the spinal cord after injury we think combinations will be necessary.”

The second trial, enrolling chronic SCI patients, begins the first of several combination trials. The MP team has known for many years that Schwann cells will fill a lesion cavity but still won’t promote nerve axons to make functional connections beyond the lesion. “From our work with rats,” she said, “we have ways now to encourage robust axon growth.” Future human trials will test adding growth factors, antibodies or cell-support matrices. “We still have work to do – it’s challenging to get an axon from the Schwann cell environment to grow past the lesion into the spinal cord environment. We’re discussing what else to test along with Schwann cells to promote axon growth and recovery.”