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New Ways to Treat Multiple Sclerosis

Thomas Gryta and Jon Kamp, Wall Street Journal, January 18, 2010

Multiple sclerosis is an autoimmune condition in which the immune system of the patient is attacking various parts of the patient's central nervous system.  Specifically, T cells recognize parts of the "insulation" that surrounds nerves, the myelin basic protein.  Loss of this insulation results in poor coordination, loss of function and eventual neuronal cell death.  Although the body possesses various repair processes, in multiple sclerosis the rate of damage is higher than the rate of repair.

One of the areas of current research is methods of accelerating the process of new myelin production.  Dr. Bruce Trapp, head of the neurosciences department at the Cleveland Clinic's Lerner Research Institute, is currently examining the natural biology of myelin by studying neurons from brains of deceased MS patients. "We know the MS brain can repair its lesions," or areas of damage, he said.  Currently Trapp, who founded a small start-up company Renovo Neural Inc., that is trying to grow and activate cells that create myelin.

Another company, Biogen Idec Inc., a Cambridge, Mass., has created a massive portfolio in MS drugs and is now seeking ways of accelerating myelin regeneneration.  Dr. Sha Mi from Biogen found that patients with multiple sclerosis have overexpression of "Lingo-1", a protein that inhibits myelin repair.  Currently Biogen is working on small molecule inhibitors, as well as antibodies to Lingo-1. 

Dr. Peter Calabresi, director of the Johns Hopkins Multiple Sclerosis Center in Baltimore, is using high-throughput screening technologies to randomly test whether medicines that are already approved by the FDA could be used for regeneration of myelin.  By growing cells in vitro that are capable of making myelin, Dr. Calabresi found that some drugs, such as an approved antidepressant, have ability to induce regeneration. 

Perhaps one of the most tantalizing approaches to remyelination is the use of stem cells.  Animal experiments have been performed with embryonic, fetal, and adult stem cells, all of which have demonstrated some degree of success.  "Stem-cell transplant in MS has been historically attractive, but has been overtaken by our understanding of how remyelination works and the potential of the brain's own stem cells," says Robin Franklin, who heads a neural stem cell program at the University of Cambridge in England.  Dr. Howard Weiner, who directs the Partners Multiple Sclerosis Center at Boston's Brigham and Women's Hospital, believes that more progress has been made at blocking the early part of the disease than on repairing damage. "My own personal view is that I think we're better attacking the pathologic processes that are causing it as opposed to rebuilding after it's happened," Dr. Weiner says.

Currently stem cell therapy for multiple sclerosis has been pioneered by two independent groups.  Dr. Richard Burt from Northwestern University in Chicago is using the approach of autologous bone marrow transplantation.  This involves extracting bone marrow stem cells, destroying the patient's immune system with chemotherapy, and subsequently readministering the stem cells in order to "reset the clock" of the immune system.  This procedure has resulted in some benefit, however, chemotherapy induces numerous side effects that many patients cannot tolerate.  The second approach is the use of fat derived stem cells.  These cells do not require the destruction of the patient's immune system, and therefore have significantly higher degree of safety.  Of the >180 patients treated with this approach, no adverse effects have been observed.  A publication describing this type of stem cell therapy and initial results in a small group of patients is available at http://www.translational-medicine.com/content/pdf/1479-5876-7-29.pdf .



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