The annual meeting of the European Committee for Treatment and Research in MS (ECTRIMS), the largest MS conference in the world, was held in Prague in October.  Previous editions of this newsletter provided research results on current and experimental MS therapies from ECTRIMS.  This newsletter will summarize advances in understanding the underlying disease process in MS.

For many years, MS was described as a disease in which nervous system injury was caused by inflammation--this is still a common explanation for the disease.  However, over the past ten years, there has been growing recognition that, in addition to inflammation, there is another important process, degeneration, which causes nervous system damage in MS.  Inflammation is thought to cause attacks and explain much of what occurs with relapsing-remitting MS. 

In contrast, degeneration, which is the slow loss of nerve cells, is believed to cause slow worsening, known as progression, and cause progressive forms of MS, which include secondary-progressive and primary-progressive MS.  An increasing number of studies are evaluating the role of inflammation and degeneration in MS—these studies relate to identifying these processes and developing therapies that specifically target these processes.

Importantly, the research results from this meeting are preliminary—the results are not considered definitive until they have been published in a medical journal. 

Identifying Inflammation and Degeneration
Magnetic resonance imaging (MRI), the standard tool for diagnosing MS, shows clear evidence for inflammation—areas of inflammation appear as “white spots” in the brain and spinal cord on MRI scans.  It is more difficult to get a clear picture of degeneration with an MRI scan.  With MRI, degeneration appears as a very slow and very subtle decrease in the size of the brain over the course of years. 

These small changes may be seen with sophisticated research tools but are difficult to detect precisely with standard MRI machines.  To improve the ability to detect degeneration, multiple new MRI techniques are being developed and were described at the recent ECTRIMS meeting—it is hoped that, in the future, these new MRI techniques may be used in day-to-day practice in order to monitor for degeneration. 

Also, at the recent MS conference, several studies reported on an entirely new way to detect degeneration.  This technique, known as OCT or optical coherence tomography, is a simple test that uses light to determine the thickness of a layer of nerve fibers in the back of the eye.  Recent OCT studies indicate that this nerve fiber layer is thinner in people with MS and that the thickness of this layer declines over time.  OCT machines are currently available and used by many ophthalmologists.  As we learn more, OCT may be an extremely helpful tool for monitoring degeneration in daily practice and for determining whether new, experimental MS therapies have an effect on degeneration.

Distinguishing Between Inflammation and Degeneration
An ongoing issue is what the relationship is between inflammation and degeneration.  Specifically, does inflammation cause degeneration or vice versa?  Or, alternatively, are these two processes separate and unrelated?  Are there forms of MS that have more of one process than the other?  The answers to these questions are extremely important because they have significant treatment implications—MS therapies will be more effective if they are given to target a specific underlying process.

Recent studies from ECTRIMS are helping to clarify the roles of inflammation and degeneration in MS.  Several studies indicate that degeneration does not occur just in people with progressive MS—some people with relapsing-remitting MS have inflammation but also, even at an early stage, have degeneration.  An ongoing, large, international research effort, known as the MSLP or the MS Lesion Project, has collected brain tissue from people with MS.  Through microscopic analysis of this tissue, four types of MS have been identified.  Two types primarily have inflammation, one type has inflammation as well as degeneration, and another type has primarily degeneration. 

New Treatment Directions
With the recognition that people with MS have both inflammation and degeneration, there are now studies of experimental therapies that are trying to specifically target these processes.  In the past, nearly all new MS therapies were designed to decrease inflammation and were tested primarily in people with relapsing-remitting MS.

A new wave of MS therapies is being developed to attack degeneration and is undergoing investigation in people with progressive forms of MS:

• A new oral MS drug, laquinimod, has been shown to decrease degeneration in an animal model of MS.
• Two large studies of people with secondary-progressive MS are now being conducted with an experimental MS drug known as MBP8298.  
• Another new therapy, erythropoietin, has produced promising results in eight people with secondary-progressive MS.  
• A large ongoing study is evaluating rituximab (Rituxan) in more than 400 people with primary-progressive MS.   
  

The Future—“Cocktails” vs “Tailored” Treatment
Our improved understanding of inflammation and degeneration has had many beneficial effects on MS research.  It has probably led to an increased number of studies for therapies that specifically target progressive forms of MS.  It has also motivated researchers to develop tools to identify and monitor both inflammation and degeneration.

There are important treatment applications of these new concepts in MS.  In the future, we may be able to determine if a person with MS has a specific form of inflammation or degeneration—treatment could then be “tailored” to that person’s specific form of MS.  Alternatively, if people with MS have both inflammation and degeneration, then a “cocktail” of multiple anti-inflammatory and anti-degeneration therapies could be prescribed.

References
More information about the research studies reported at the ECTRIMS meeting may be found at:  www.akm.ch/ectrims2007/.