Multiple Sclerosis Newsletter
Northern Colorado Edition

June - July 2005

Research Updates

TROY: A NEWLY IDENTIFIED STOP SIGNAL IN THE PATHWAY FOR NERVE REGENERATION
Michelle D. Jones-London, PhD 2005 (Mar. 9)
Natl. Insti. Neuro. Dis&Stroke

One of the major puzzles in neuroscience is how to get nerves in the brain and spinal cord to regrow after injury. A new study has identified a protein, TROY, that inhibits nerve cell repair and plays a role in preventing nerve regeneration. This finding is an important step in developing new methods for treatment of spinal cord injury, stroke, and regenerative nerve disorders such as multiple sclerosis (MS).

Most of the cells in the human body have the ability to repair themselves after injury. However, neurons in the central nervous system (CNS) are unable to regenerate their injured axons. One of the major obstacles to regeneration in the adult CNS is the presence of inhibitory molecules that are associated with myelin, a fatty coating that forms a sheath around nerve cells. Research in recent years has focused on identifying the chain of events that prevents regeneration.

Part of the inhibitory or “braking” machinery that stops nerve regeneration is Nogo, a protein normally found in myelin. Studies have suggested that a necessary partner or co-receptor to Nogo is a protein called p75, which is common in the developing nervous system but decreases during adulthood. However, while most neurons in the central nervous system do not have p75, these neurons still demonstrate myelin inhibition and cannot repair themselves. In the new study, Dr. Zhigang He and colleagues from The Children’s Hospital of Harvard Medical School in Boston asked, “Why do neurons without p75 still fail to regenerate after injury?” Their findings appear in the February 3, 2005, issue of Neuron. This research was funded in part by the National Institute of Neurological Disorders and Strokes (NINDS).

“We hypothesized that either these neurons without p75 have a completely different mechanism to prevent regeneration , or that a different version of the protein exists,” says Dr. He. “This investigation led us to the newly identified TROY protein, a member of the same receptor family as p75. While TROY has a similar action to the p75 protein, it is widely expressed throughout the CNS. TROY also has a well researched biochemical pathway that could help us to possibly target new strategies for clinical therapy.”

This study is the first to show that TROY is a critical player in blocking nerve regeneration. Although the research does not eliminate the possibility that other molecules are also involved in regeneration, the study helps scientists to understand how myelin inhibition may be regulated. The finding that more than one protein may be involved in myelin inhibition adds a new level of complexity to designing therapeutic strategies for treating CNS injury.

”Designing a therapeutic strategy to block myelin inhibition would be an efficient way to promote regeneration. This research may provide important insights into development of future treatment for spinal cord injuries,” says Dr. He.

Researchers caution that any strategy to alter the inhibitor proteins would need to be carefully designed. Since both p75 and TROY are expressed in many types of cells in the CNS and are also involved in inflammatory responses, simply blocking these proteins could lead to many undesirable side effects.

The discovery of the TROY protein enhances understanding of nerve injury and provides a piece in the puzzle of CNS nerve regeneration. Investigators hope this information will point to ways to stimulate nerve repair in the brain, which is vital for restoring functions in persons with MS, spinal cord injury, stroke and other CNS injury conditions.

The NINDS is a component of the National Institutes of Heath within the Department of Health and Human Services and is the nation’s primary supporter of biomedical research on the brain and nervous system.

Reference: Park JB, Yiu G, Kaneko S, Wang J, Chang J, He Z. “A TNF receptor family member, TROY, is a coreceptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors,” Neuron, February 3, 2005, Vol. 45, pp. 345-351.

PROMISING MULTIPLE SCLEROSIS TREATMENTS ON THE WAY
Mark Babineck (Source: Reuters Health 2005-04-12 17)

HOUSTON (Reuters) – The suspension of sales of promising multiple sclerosis drug Tysabri earlier this year was devastating to disease sufferers, but it has opened a window of opportunity to alternative treatments.

Among the therapies in the pipeline is Tovaxin, a PharamaFrontiers Corp., product developed at the Baylor College of Medicine in Houston. “Tovaxine is a fascinating concept,” said Dr. Edward Fox, director of the Multiple Sclerosis Clinic of Central Texas in Austin. “It’s basically a way of immunizing yourself against your own bad blood cells. It’s much more a magic bullet.”

Tysabri was considered the leading therapy for MS until February, when maker Biogen Idec suspended sales after a patient died from a rare brain infection. Two other patients have been diagnosed with the infection since then. Biogen told Reuters last week it still hopes to bring back Tysabri for patients who do not have suppressed immune systems.

“It still is a remarkably effective drug and a tolerable drug and it may yet come about as an MS drug,” Fox said. “They may find it safe as a single drug, but not in combination with other medications. It’s still an open story.”

There are other treatments farther on the horizon, Fox said, including monoclonal antibodies aimed at selective portions of the immune system and a pill that could replace shots, intravenous drips and other more invasive techniques.

PharmaFrontiers is hopeful Tovaxin can fill the void sooner. Currently, in U.S. Food and Drug Administration trials, the treatment sparks an autoimmune reaction against the rogue Tcells that are thought to attack the protective sheath around nerve fibers, causing MS.

Tovaxin is not a drug. Rather, it is a treatment that redirects a patient’s own T-cells, meaning it is developed specifically for each case. “It’s always going to be an individualized treatment,” PharamaFrontiers Chief Executive Officer David B. McWilliams said. “It seems like the disease is individualized. One size does not fit all.”

PharmaFrontiers, based near Houston, acquired Tovaxin when it acquired Opexa Pharmaceuticals Inc. last November. If Tovaxin is approved, PharmaFrontiers wants to serve MS patients across the nation and around the world, likely meaning facilities in Europe and Asia. That sort of expansion will require cash and McWilliams leaves open the possibility his company could be acquired by a bigger fish some day.

“These things require continual amounts of funding,” he said. “At some point in time we’ll seek out a European partner and a Far East partner to help pay for parts of this. It clearly will require some more money.”

PROVIGIL DOESN’T HELP MS FATIGUE BUT ASPIRIN MIGHT
Dr. Bruno Stankoff & Dr. Dean M. Wingershuk
Neurology, April 12, 2005

NEW YORK (Reuters Health) – Provigil, a drug used to treat the sudden-sleep disorder narcolepsy, does not affect fatigue experienced by people with multiple sclerosis (MS), results of a trial suggest.

However, a separate study found that aspirin may be of some benefit. Both studies appeared in the medical journal Neurology.

Two small pilot studies recently showed a positive impact of Provigil, technically known as modafinil, on MS-related fatigue, note Dr. Bruno Stankoff, at Hospital de la Salpetriere in Paris and members of the French Modafinil Study Group, in the first study.

To further investigate, the group randomly assigned 56 patients scoring 45 points or more on a fatigue scale to Modafinil, and 59 to an inactive placebo.

Both groups experienced decreased fatigue during the 35-day trial, but change in fatigue scores did not differ significantly between the two groups.

In the second study, Dr. Dean M. Wingerchuk and colleagues point out that some MS patients using aspirin for other purposes report reduced fatigue.

In crossover trial, 30 patients with MS-related fatigue took either aspirin twice daily or placebo for 6 weeks in random order, separated by a 2-week “washout” period. Average scores on one fatigue scale were lower during aspirin treatment (38.1 versus 42.5), but responses did not differ significantly on two other scales.

Commenting in a related editorial, Drs. Steven R. Schwid of the University of Rochester, New York, and T. Jock Murray of Dalhousie University in Halifax, Nova Scotia, observe that “until we make progress in distinguishing fatigue from other MS symptoms, in identifying its mechanisms and in measuring it accurately, we will not make substantial progress in treating this disabling symptom.”

STUDY REPORTS ASSOCIATION BETWEEN SMOKING AND PROGRESSION OF MS
Miguel A. Herman, MD et al., Brain (March 9, 2005)

Summary: Researchers funded by the National Multiple Sclerosis Society report that smoking was associated with a moderate increase in the risk of developing MS in a study of 201 people with MS and 1913 people without MS; they also found an association between smoking and risk of MS progression in 20 people whose MS progressed during the study’s follow-up period. [sic]selected up to 10 controls without MS for each individual with MS, for a total of 201 people with MS and 1913 controls. Smoking status was obtained from the database and compared between the groups. To assess the association between smoking and progression of MS, they followed 179 people who had been diagnosed with relapsing-remitting MS for an average of 5.3 years.

The proportion of people who had ever smoked was 45.8% among people with MS and 39.4% among controls. Data on the duration or intensity of smoking were not obtained. People who smoked had a moderately increased risk of developing MS compared with those who did not smoke.

Of the 179 people with relapsing –remitting MS, 20 people (11%) converted to a progressive course during the period of follow-up. The risk of developing secondary-progressive MS was more than three times higher in smokers than in non-smokers.

Conclusion: This study confirms previous findings of an association between smoking and an increased risk for MS. The study is also the first to show that smoking may be a risk factor for disease progression, however, this association was shown in a small number of people – the 20 people who progressed during the observation period. Further study is necessary to confirm this association in larger numbers of peple and to explain the possible underlying mechanisms that could be responsible for a link between smoking and the development, or progression, of MS.

WHAT IS ORIENTAL MEDICINE?
Margaret Helenschild, B.S., Lic. Ac., NCCAOM
The Healing Path Magazine

Oriental Medicine has a rich and varied history. It developed in many different countries in the Orient and blossomed with many different flavors. The most familiar modality in the Western world is acupuncture.

It’s evolution in each region depended on the climate, the local culture, the specific talents and interests of the Masters in those regions, and the types of diseases that were being experienced as it evolved. As a result, we have many different schools of Oriental Medicine today, each with its unique perspective. Even with many perspectives in OM, there are threads that run through all of OM. One is that it is based in the observation of Nature and a person’s relationship to it. Nature is reflected in a person’s well being; physical, mental, emotional and spiritual. When there is a part that is out of balance, it results in disharmony, which can manifest in the physical, mental, emotional, and/or the spiritual domains.

Another common thread is the understanding that the whole person IS the picture, not just the disease itself. This might be likened to a large jigsaw puzzle.

On initial observation, it is a boxful of unrelated pieces. However, as the pieces are put together, a cohesive picture begins to unfold. This is true of OM. When viewed individually, the pieces seem to make no sense. However, as they are placed together, they form a context, and the “whole picture” becomes clear.

YIN and YANG

Yin and Yang are polar opposites, interdependent, and relative. Think of them as defining one another. You cannot have the concept of up without the concept of down, the concept of heat without the concept of cold. In the relationship of things, something defined as Yin would be cooler, more solid, more inward, more downward, more heavy, and more at rest than Yang. Yang would be warmer, less solid, more upward, lighter, and more moving than Yin. When a body is in healthy balance, or homeostasis, Yin and Yang regulate one another. For example, when the body becomes too warm (too Yang), the cooling (Yin) mechanisms kick in to cool things down. When a person is out of balance, these mechanisms can fail to regulate one another, and disease may result.

It is a defining, diagnosing, and treating imbalances before the manifest as disease that OM shines. Picking up the subtle clues and treating imbalances before a person becomes ill is the basis of all OM. In the ancient text “The Yellow Emperor’s Inner Classic” it states “Treating disease after it has manifested is like waiting to dig a well until one is thirsty.”

However, in the modern world, that is exactly how most of us are. We wait until we have symptoms of illness before we are willing to change our lifestyles including diet, exercise, stress management and rest. The good news is that OM is a very effective tool to reverse many disease processes even after they have manifested. We can still restore balance in our lives and retain our health using OM. Acupuncture and Chinese herbal medicine in conjunction with healthy lifestyle changes can bring your life into the optimal healthy balance you really want.

In terms of the presentation of MS symptoms, as we know, they will vary greatly from person to person. It would come as no surprise, then, that when addressing MS with acupuncture or Chinese herbal medicine, the treatment for each person will be very different.

A partial list of conditions that are successfully treated with Oriental Medicine.

Anxiety, Joint Pain, Arthritis, Menopausal Syndrome, Back/neck pain, Menstrual Disorders, Chronic fatigue, MS, Digestive problems, PMS, Emotional Imbalances, Respiratory Problems, Headaches/Migraines, Sinusitis, Immune Issues, Stress Disorders, Insomnia, Traumatic Injuries

(portions of this article were previously presented in The Healing Path Magazine)

BIO: Margaret Helenschild has been practicing acupuncture and Chinese herbal medicine in Ft., Collins since 1984. She can be reached at 224-4787 if you have questions of how acupuncture would be of benefit for you or a loved one.

NERVOUS SYSTEM REPAIR AND PROTECTION INITIATIVE ROLLING BACK THE RAVAGES OF MS
Nat. MS Soc. 2005

What if we could actually reverse the damage that MS causes, restoring function to those who have been living with the disease for years? Recent scientific advances in many different fields are now, for the first time, coming together to bring the dream of protecting and repairing brain tissue and restoring function within our grasp. The Society now targets this vital quest with a program that could dramatically impact future disease management, improve the lives of the estimated two million people worldwide living with MS, and could ultimately lead to a cure.

A specially convened National MS Society Task Force determined that the best way to accelerate nerve tissue repair is to bring together the appropriate clinical specialists and basic laboratory scientists to form partnerships to conduct all elements of the study, from basic research to human clinical trials.

Collaborating to make tissue repair and protection a reality.
To ensure the speediest results, the task force recommended that the Society fund as many centers as can meet the extensive expectations of the project. This invites a range of creative approaches and ensures that trials can be replicated and verified in multiple locations. A worldwide “request for proposals” for this topic has been circulated, and many institutions around the world have indicated their interest. We will know in June 2005, after a thorough peer-review process, which and how many partnerships will be launched.

The task force established these aggressive goals for collaborative groups seeking our funding:

*Move tissue repair and protection studies out of the test tube and laboratory mice into human model testing.
*Monitor tissue repair and protection in humans in a non-invasive fashion to determine whether the treatment is working.
*Ensure that successful repaired issue is protected from the future ravages of multiple sclerosis.

Challenges and the future.
Leading researchers now believe that treatments aimed at protecting nerves and rebuilding myelin and damaged nerve fibers are on the horizon. This unique effort – unparalleled anywhere in the world – will not come cheaply. We are preparing to give the largest grants (up to $5.5 million/award) ever offered by any funding agency for nerve repair. This funding level will allow scientists to form new alliances, to re-tool and hone their scientific and clinical skills for this very specific effort, to attract more “heads and hands” to the problem, and to utilize the best available technology and develop needed new technologies to achieve our goals.

Scientists and clinicians have a challenge to make tissue repair and protection a reality. Our challenge is to ensure they get the funding to succeed.

TREATING LEARNING IMPAIRMENTS IMPROVES MEMORY PERFORMANCE IN MULTIPLE SCLEROSIS: A RANDOMIZED CLINICAL TRIAL
M.S. Vol. II, Issue 1 (Feb. 2005)

In this clinical trial of 29 patients with MS and learning difficulties, participants were randomized to eight sessions of the Story Memory Technique (experimental group) or eight sessions of memory exercises (control group). Assessment was completed at baseline, immediately after and 5 weeks after intervention.