Mayo Clinic Identifies Potential New Therapeutic Target for Progressive Multiple Sclerosis

Tuesday, September 23, 2008

A new Mayo Clinic study has found that two particular enzymes were elevated in patients with progressive multiple sclerosis (MS). The levels of these enzymes also were associated with the patients' levels of disability. These findings give researchers new hope in developing a therapy for patients with progressive MS.

VIDEO ALERT: Additional audio and video resources, including excerpts from an interview with Dr. Scarisbrick describing the research, are available on the Mayo Clinic News Blog.

This study will be presented at the American Neurological Association annual meeting in Salt Lake City on Sept. 23, 2008.

Mayo Clinic provides care for nearly 2,500 patients with MS each year. MS is a disease of the central nervous system that includes the brain, spinal cord and nerves. MS is called a demyelinating disease because it results from damage to myelin, the insulating covering of nerves. It occurs most commonly in those between the ages of 20 and 40, and is the most frequent neurological disorder in young adults in North America and Europe. Approximately 330,000 people in the United States have MS. Symptoms include loss of muscle coordination, strength, vision, balance and cognition. In patients with progressive MS, these symptoms do not decrease in intensity, while patients with relapsing/remitting MS may experience partial or total recovery from symptoms.

"The current MS therapies are most effective for relapsing/remitting MS, with fewer options for patients with progressive MS," says Isobel Scarisbrick, Ph.D., a Mayo Clinic neuroscientist and a lead author of this study. "It's also sometimes difficult to diagnose which type of MS a patient has, and it's important to treat these patients differently."

To help distinguish between the types of MS and identify a therapeutic target for progressive MS, Dr. Scarisbrick and a team of Mayo Clinic researchers studied five different Kallikreins, or secreted enzymes, in patients with MS. The team tested the level of each Kallikrein in the blood of 35 patients with MS and 62 healthy patients. They found that Kallikrein 1 and Kallikrein 6 were significantly elevated in patients with progressive MS. Additionally, the higher the level of Kallikrein 1, the higher the patient's level of disability, which was measured by expanded disability status score. The Mayo Clinic team also looked at the effects of these enzymes on neurons isolated from the brains of mice and found that both Kallikrein 1 and Kallikrein 6 caused significant loss of neurons and injury to axons.

"We will continue to study how Kallikrein 1 and Kallikrein 6, either separately or together, play roles in neuron injury and how it occurs in patients with progressive MS," says Dr. Scarisbrick. "Eventually, we hope to determine a way to target these enzymes with therapies that will benefit patients with progressive MS."

Other members of the Mayo Clinic research team included Rachel Linbo, D.P.T.; Alexander Vandell, Pharm.D.; Nadya Larson, Ph.D.; B. Mark Keegan, M.D.; Diane Sneve; Claudia Lucchinetti, M.D.; and Moses Rodriguez, M.D. Other contributors included Eleftherios Diamandis, M.D., Ph.D. of Mount Sinai Hospital, New York, NY, and Sachiko Blaber and Michael Blaber, Ph.D., both of Florida State University, Panama City, FL.

This study was funded by a grant from the National Multiple Sclerosis Society and the Craig H. Neilsen Foundation.

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