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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 at: http://newsblog.mayoclinic.org/2008/09/ ... ic-target/.
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.
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."
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Kallikreins are associated with secondary progressive multiple sclerosis and promote neurodegeneration.
Biol Chem. 2008 Jun;389(6):739-45.
Program for Molecular Neuroscience, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. email@example.com
Tissue kallikrein KLK1 and the kallikrein-related peptidases KLK2-15 are a subfamily of serine proteases that have defined or proposed roles in a range of central nervous system (CNS) and non-CNS pathologies. To further understand their potential activity in multiple sclerosis (MS), serum levels of KLK1, 6, 7, 8 and 10 were determined in 35 MS patients and 62 controls by quantitative fluorometric ELISA. Serum levels were then correlated with Expanded Disability Status Scale (EDSS) scores determined at the time of serological sampling or at last clinical follow-up. Serum levels of KLK1 and KLK6 were elevated in MS patients (p<or=0.027), with highest levels associated with secondary progressive disease. Elevated KLK1 correlated with higher EDSS scores at the time of serum draw and KLK6 with future EDSS worsening in relapsing remitting patients (p<or=0.007). Supporting the concept that KLK1 and KLK6 promote degenerative events associated with progressive MS, exposure of murine cortical neurons to either kallikrein promoted rapid neurite retraction and neuron loss. These novel findings suggest that KLK1 and KLK6 may serve as serological markers of progressive MS and contribute directly to the development of neurological disability by promoting axonal injury and neuron cell death.
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