Researchers join to launch groundbreaking clinical trial for MS treatment

Researchers at Case Western Reserve University, Cleveland Clinic and University Hospitals Seidman Cancer Center have come together to launch a new clinical trial of an experimental treatment for multiple sclerosis (MS). The groundbreaking study will test the feasibility and safety of using the body’s own stem cells to treat MS.

The clinical trial builds off years of work done by Arnold Caplan, professor of biology, and Robert Miller, a professor of neurology and associate dean for research at the School of Medicine.

In patients with MS, the immune system abnormally attacks the central nervous system, causing damage to the nerve cells and their protective myelin sheath. The body has mechanisms that attempt to repair this damage; however, in MS, the repair cannot keep pace with the ongoing damage.

The Phase 1 trial involves harvesting a patient’s mesenchymal stem cells (MSCs), which are primitive cells in the bone marrow, culturing them in a laboratory, and then injecting the MSCs intravenously back into the patient to see if the procedure is safe, decreases disease activity and leads to improved repair.

The research team is headed up by Jeffrey Cohen of the Cleveland Clinic’s Mellen Center for Multiple Sclerosis Treatment and Research, and is funded by a $2.75 million, four-year grant from the United States Department of Defense and a $1 million grant from the National Institutes of Health. Cohen is director of the Mellen Center’s Experimental Therapeutics Program and professor of medicine (neurology) in the Cleveland Clinic Lerner College of Medicine of the Case Western Reserve University School of Medicine.

Stanton Gerson, director of the UH Seidman Cancer Center and director of the National Center for Regenerative Medicine (NCRM), said, “This trial in MS is one of the most innovative trials of MSCs as it truly investigates both the clinical aspects as well as the science of what these cells do and how they may confer therapeutic benefit to recipients.”

Caplan and Miller, members of the clinical trial’s advisory committee, laid the groundwork for the current clinical trial. They discovered that in mice that have a form of MS, human MSCs promote healing of damage and protect against an autoimmune response.

Caplan had long studied mesenchymal stem cells, adult stem cells culled from bone marrow, as building blocks for engineered tissues and organs. Miller had spent his career studying neural development, with a focus on treatments for multiple sclerosis.

They met at a Research Showcase in 2003 and decided they should work together.

“We knew MSCs differentiate into bone and tendon and other connective tissues, but we were just beginning to understand they also provide healing instructions at the site of injury,” Caplan said.

Miller was looking for therapies for diseases that attack myelin, the protective coating that wraps nerves’ long axons.

In MS, the immune system attacks the myelin and the exposed nerves’ intricate wiring can be damaged. The result: nerve signals can be blocked, causing loss of balance and coordination, cognitive ability and other functions. Losses may become permanent.

“What the nerves need is repair and protection,” Miller said.

The researchers thought molecules MSCs make could be useful, but, “It was a shot in the dark,” Caplan said.

After some promising in vitro results, Caplan provided Miller with MSCs from human donors. Miller injected them into mice that had a version of MS.

“The mice got better, and quickly,” Miller said. And the animals didn’t reject the human cells or show negative effects.

The mice had fewer and smaller lesions on their myelin compared to control mice.

Miller and Caplan found evidence that the MSCs produced a barrier that blocked the autoimmune response and blocked formation of scar tissue, which would otherwise permanently halt signals. In addition, the cells produced molecules that enhanced regeneration of the damaged axon and rewrapping of the myelin around the axon.

Continued monitoring showed that one shot provided protection from the recurring disease for months.

The Phase 1 study, which will take two to three years to complete, will involve 24 patients with relapsing-remitting or progressive MS who have moderate to severe disability. If this trial demonstrates that MSC transplantation is safe, future studies will more definitively assess the efficacy of this therapy in MS. The study has already enrolled four patients, and the team expects to begin to report their initial findings over the next 1-2 years.

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