Printer Friendly

What's new? Researchers venture down novel pathways in MS.

Although six therapies are currently FDA-approved to treat MS, the search goes on for more effective drugs, treatments that will address disease progression, and strategies to repair or protect against nervous system damage. Scientists are searching high and low for therapeutic targets, and this search is yielding some novel approaches with high potential for providing the next generation of therapies for MS.

What lies within

An ideal target for stimulating repair in MS would be one that already exists in the body and could be tweaked to promote an innate ability to protect or repair the nervous system. Because, in fact, there is evidence of repair in areas of damage in people with MS, but for some reason these capabilities fail to keep up with the pace of the disease's attack. At the World Congress of MS Research (see below) Catherine Lubetzki, MD, PhD, and colleagues (Hopital de la Salpetriere, UPMC, Paris, France) reported on a molecular family that might fit the bill--semaphorins. (Abstract #23)


Semaphorins are a large family of proteins that act as guidance molecules in the developing nervous system. Some, like semaphorin 3F, put out signals to attract cell migration, while others, like semaphorin 3A, put out signals that inhibit cell migration.


Dr. Lubetzki's team has found that both of these molecules are increased within areas of tissue damage in people with MS. This may mean that while semaphorin 3F is attracting immature myelin- making cells to sites needing repair, increased signals from semaphoring 3A are preventing repair from occurring. Learning more about these signals, and how they might be manipulated, may lead to novel repair strategies in the future.

Dampening nerve excitement

The immune attack on the nervous system in MS plays out in many ways. Recent results indicate that glutamate, a neurotransmitter (a substance released from nerve cells to transmit nerve impulses to another cell) may play a role in the death of myelin-making cells by overly exciting the central nervous system.

John W. Rose, MD, is investigating, with funding from the National MS Society, the steps that lead from the immune attack in MS to glutamate's actions in the central nervous system. Dr. Rose is looking at a molecule active in inflammation, COX-2, which may stimulate glutamate "excitotoxicity." They have previously shown that COX-2 is active in myelin-making cells obtained from people with MS.

Dr. Rose's team reported exciting results at the World Congress, in which they administered a COX-2 inhibitor (similar drugs are approved to treat arthritis) to mice with an MS-like disease. Treatment decreased myelin damage, and more importantly, decreased the stimulation of glutamate and the death of myelin-making cells. These studies may provide evidence for future clinical investigations of COX-2 inhibitors in MS.(Abstract #P164)

Changing batteries in nerve cells

Injury to axons--the fibers that transmit nerve signals from one nerve cell to another--is now recognized as an important contributor to progressive neurologic dysfunction in people with MS. Some research suggests that the MS disease process causes excessive amounts of calcium to build up within the axons, causing destruction. Preliminary research has revealed that mitochondria--the energy factories of cells--play a key role in calcium balance within axons. Mitochondrial dysfunction may thus be an important player in the progression of MS.


With this in mind, Societyfunded teams are working on this area. Dennis Bourdette, MD (Oregon Health & Science University) is the leader of a Collaborative MS Research Center Award aimed at investigating the role of mitochondrial dysfunction in nerve fiber damage in MS. Dr. Bourdette reported at the 2008 Society for Neuroscience meeting that deactivating cyclophilin D--a key protein in mitochondria--was crucial to keeping the balance of calcium steady within nerve cells. (Abstract #51.2/Y6)

These studies could suggest therapies that reverse mitochondrial dysfunction, in hopes of protecting axons from degeneration and thereby preventing disease progression.

Blood passage

Research is increasing on how the blood-brain barrier (BBB), a lining of cells that should protect the brain from intruders, ends up breaking down in people with MS. Some of this research is focusing on blood proteins that may leak into the brain.

Society grantee Katerina Akassoglou, PhD, and postdoctoral fellow Ryan A. Adams, PhD, and colleagues previously reported findings on fibrinogen, a protein essential for blood clotting. (The Journal of Experimental Medicine 2007;204:571-82) The team genetically engineered mice in which fibrinogen was not activated, and found that inducing MS-like disease in these mice resulted in less myelin damage and less severe symptoms. More recently, Dr. Akassoglou has shown that fibrinogen that leaks into the spinal cord actually inhibits the growth of neurites, which are extensions of nerve cells. (Proceedings of the National Academy of Sciences U S A 2007;104:11814-9) Targeting the effects of fibrinogen and similar clotting factors may prove to be important to preventing nerve damage in MS.

As the search for these novel targets continues, the results are yielding much promise for the development of novel strategies to treat people with MS.
COPYRIGHT 2009 National Multiple Sclerosis Society
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2009 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Title Annotation:Research Now; multiple sclerosis
Article Type:Report
Geographic Code:1USA
Date:Mar 22, 2009
Previous Article:Picture it: why researchers need better imaging techniques.
Next Article:No overall link found between hepatitis B vaccine and MS.

Related Articles
MS researchers share findings in Baltimore. (National MS Society).
Vitamin D and multiple sclerosis.
Medical, pyschological, social, and programmatic barriers to employment for people with multiple sclerosis.
Nervous system repair: the next frontier in MS research.
What researchers are doing for people with MS now.
New mouse model gives important insights into emergence, progress of multiple sclerosis.
How Dr. David Miller revolutionized our understanding of MS.
The impact of pain and other symptoms on quality of life in women with relapsing-remitting multiple sclerosis.

Terms of use | Privacy policy | Copyright © 2018 Farlex, Inc. | Feedback | For webmasters