Transcript of NMSS Webcast on Gender, Genes, and Complimentary and Alternative Therapies in Multiple Sclerosis
Originally presented on May 14, 2002
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Moderator: This is the National Multiple Sclerosis Society’s North American Education Conference; Reaching for New Frontiers in MS Research. I’m Rick Turner and I will be your host for tonight’s program. We’ll begin with a welcome from Mike Dugan, CEO of the National MS Society, followed by presentations from our expert panel. Our three nationally recognized presenters will describe current research in the areas of gender, genetics, and complementary and alternative therapies in MS. Following their presentations, the program will move into a live, interactive question-and-answer segment. It is now my pleasure to introduce the President and CEO of the National Multiple Sclerosis Society, retired Air Force General Mike Dugan.
GENERAL DUGAN: Thank you, Rick, and thanks to all of our viewers for joining us today for an exciting look at new frontiers in MS research. We are delighted tonight to welcome people with MS and their family members, and professionals, at hundreds of broadcast sites hosted by National MS Society chapters and by our new partner in this program, the Multiple Sclerosis Society of Canada. A very special welcome, and “bien venue extraordinaire”, to our friends and colleagues from our great neighbor to the north. We also welcome from all over the world those who are joining our program via the Internet. I would like to take a minute to thank today’s platinum sponsor, Teva Neuroscience, whose unrestricted educational grant has made this program possible. Our thanks are also extended to HEALTHSOUTH and the many other facilities that have provided space for viewing this program, and to the hundreds of volunteer site facilitators.
This is an exciting time in the world of MS research. Technological and scientific advances that we could not have dreamed of even a decade ago now bring new hope to our fight against MS. Much of the work you will learn about here could not have been endorsed just a few years ago. Let’s hear from some of the members of the Society’s Medical Advisory Board, as they talk about new frontiers in MS research.
“I’m really happy to tell you that there are many exciting new frontiers in MS Research.” Aaron Miller, M.D.
“We’re making progress in many different areas of basic science, like immunology, genetics, and the infectious disease aspects, so I think all of these are moving forward as a broad front and that they’re all frontiers to follow closely.” James Bowen, M.D.
“A really exciting frontier for people with MS today, is the work that’s being done not only on individual treatments for MS disease modifying agents, but on combinations of agents—medications that can be taken together.” George B. Garmany, M.D.
“One new, exciting thing that is developing is an awareness that MS occurs not only in adults, but also in children and adolescents. By identifying and characterizing this group, we have an opportunity to make significant headway in understanding the processes that lead to the development of MS.” Lauren Krupp, M.D.
“Clearly, as we learn more about the immune system and learn how to modulate the immune system, we’re learning how to control the disease, multiple sclerosis.” Randy Schapiro, M.D.
“In fact, what was once science fiction, is now scientific fact. There are stem cells that exist in adult humans that can develop into nervous system cells.” Andrew Goodman, M.D.
“I think our current disease modifying therapies are very exciting, but they don’t reverse fixed damage. We now are looking at very exciting new techniques that can actually reverse some of the damage. That offers great hope to many, many MS patients out there.” Patricia Coyle, M.D.
“There has been a tremendous revolution in genetic research and all kinds of new technological advances that enable better analysis of genetic material. We think this is going to bear fruit with regard to MS.” Aaron Miller, M.D.
“There is research going on in each of these areas that makes it so exciting now. I think in the future we’re going to be able to manage multiple sclerosis much more effectively.” Randy Schapiro, M.D.
”I think we’re going to see some of these translate into potentially useful therapies.” Aaron Miller, M.D.
GENERAL DUGAN: Like our Chief Medical Officer, Dr. Aaron Miller, and his colleagues on the Medical Advisory Board, I too am hopeful and optimistic that our research efforts will pay off -- dollars in current and future commitments to over 300 MS research projects.
And our search for new answers will continue, until we can say that we have, indeed, ended the devastating effects of multiple sclerosis. Now, let me turn back to our moderator, Rick Turner, to begin our program.
Moderator: The purpose of today’s satellite program and Web cast is to explore with you some new frontiers in MS research. You will hear about important research initiatives in the areas of genetics and gender differences that help us understand who gets MS and why. This new knowledge may expand treatment options and bring us closer to a cure or even prevention of this disease.
You will also hear about the sometimes-rocky—even antagonistic—relationship between mainstream medicine and the world of complementary and alternative medicine, as well as ongoing efforts to integrate the two approaches into a more comprehensive approach to health and wellness for those living with MS.
Moderator: And now, our panel presentation will begin with the subject of genetics. The relationship between genetics and MS is a common concern for individuals and families living with multiple sclerosis. While MS is not hereditary, such as hair color or eye color, for example, a person who has a parent or sibling with MS has a significantly greater risk of developing the disease than a person with no MS in the family. Scientists theorize that MS develops in individuals who are born with a genetic predisposition to react to some environmental or infectious agent. Exposure to that agent then triggers the autoimmune response. Research has begun to identify the genes that seem to be involved in this process.
Tonight we will hear from a leading researcher in this exciting area, Dr. Stephen Hauser, Professor and Chair of the Department of Neurology at the University of California in San Francisco. Dr. Hauser will give a brief overview of research in genetics and share with us his own research in this valuable area.
Dr. Hauser: I’m delighted to have been asked today to speak with you about genetics and MS. Here you can see a photo of two teddy bears that were originally identical. One had the good fortune to remain on the shelf, whereas the other became the favorite companion of a two-year-old boy. Thus, their fate was quite a bit different.
It’s really the same with MS. Both the genetic background—how we are put together, and the environment—what we’re exposed to, determine our risk for MS, and maybe also the form that the disease takes.
Here you can see a photo from inside a human cell, illustrating our chromosomes. Our bodies are made of cells, and inside each, contained within the nucleus, lives this material of heredity. Humans have 46 chromosomes inside each cell—a set of 23 from each of our parents. So we really have two copies of each chromosome. A gene is a piece of a chromosome containing information for the production of a protein, which has a specific function in a cell. As humans, we have 35,000 genes and 46 chromosomes. It’s humbling that mice have the same numbers of genes and chromosomes. Nonetheless, the essence of our humanity and our species is encoded in this material.
Genes influence many things about us that define our individuality. Our hair color, our appearance, whether or not we have stage fright, whether or not we have a great jump shot or are relegated to the audience. More importantly, genes influence our lifespan, health, and susceptibility to many diseases including MS. I mentioned earlier that we all have two copies of each chromosome and gene. Gene mapping takes advantage of the fact that each parent chromosome we inherit usually contains rearranged pieces of similar chromosomes—in other words, ahybrid of the original rather than complete copies of our parents’ chromosomes. This phenomenon, termed recombination, can be explored to search for regions of chromosomes that are inherited, along with diseases that are carried on them.
And here in this cartoon, you can see a family where father and mother are on the top and five children are on the bottom. Father is bowlegged. You can see that three of the children are also bowlegged. Each of the three children has inherited either the orange chromosome or a piece of the orange chromosome from the father. Thus, if this finding is verified in other similar families, we can conclude that the gene for bowleggedness is on the orange chromosome and more specifically, can be mapped to that little region in the middle of the orange chromosome present in the third child who is bowlegged.
Now, each of our genes or chromosomes is made up of simple building blocks called nucleotides, of which there are only four types. The sequence of these building blocks, or our DNA, determines the function of the gene. Furthermore, individual genes come in different flavors or types, determined by small differences in the sequence. Gene mapping involves the search for these small sequence differences that cause disease. Here on the slide, you can see an example of a small sequence difference that can be used to map where MS genes might reside. There are two individuals on the top of the slide who are genetically mapped. And you can see in the yellow bar, that the top individual has a DNA sequence that has a T in the third position, whereas the bottom individual has a C. Now that difference can be found to map within families and if we identify that a T is present in all of the individuals who have MS, this would suggest that the mutation that created the T also conferred susceptibility to the disease.
This kind of work, which used to be very arduous, is now becoming increasingly simple. This is because of rapidly developing new technologies, and that momentous day last February when the structure of the genetic code of humans was reported. Now this initial gene map was derived from only five individuals belonging to different ethnic groups. Current gene mapping efforts on a national and international scale, want to define exactly how many differences exist in all humankind. Our task is to find the sequence differences that confer susceptibility to MS. And to do so, we’ve been engaged for 15 years in a collaborative effort to map the genes that predispose people to MS. Similar efforts have been underway in Canada, the United Kingdom, and elsewhere. These studies are performed by collecting large numbers of families who are at increased risk for MS—meaning that two or more individuals are affected. The type of MS that is present is carefully charted and blood samples taken so that DNA can be prepared and stored in a repository or library. Thanks to the National MS Society, these materials are now available to interested investigators worldwide.
And in this slide, you can see one family who has volunteered for participation in this study. On the right, you can see two brothers and a sister, all of whom have MS, but in each of whom the form of MS appears to be different. If any of you in the audience belongs to such a family and wishes to participate in these genetic studies, we’d be most grateful if you would contact us at 1-866-MS GENES. That’s 866, M-S-G-E-N-E-S.
Initial screens of the entire genome to map MS genes were first completed in 1996. Follow-up screens became available in 2000 and 2001, and even more refined maps are now in the works. These screens have identified the location of eight, and perhaps as many as 13 regions on different chromosomes that we believe are important to MS.
Let me speak about two genes of particular interest that have now been identified. The first is an HLA gene. Now HLA genes function as master switches of the immune system. They bind to proteins and thereby turn on inflammation. Of all of the flavors of HLA genes, of which there are many hundreds, only one flavor—termed DR2—is relevant to MS. And we believe that DR2 is important to MS because it binds a piece of a myelin protein—termed MBP—in a very tight fashion, making this myelin protein incite inflammation in the brain. Now only 50 percent of people with MS have the DR2 flavor of the MS gene. Thus a key question that we need to answer is whether a treatment response to MS therapy is influenced by whether or not one has this gene. This is really quite important because Copaxone® (glatiramer acetate)—one of the major therapies that we use for MS—was originally designed to block the binding of the MBP protein to DR2.
The second gene is called ApoE. This gene is on chromosome 19 and binds cholesterol. ApoE comes in three flavors, designated 2, 3, and 4. It’s been learned that individuals with ApoE who have nervous system injuries from trauma, Alzheimer’s disease, or other causes, heal less well than do people fortunate enough to have ApoE2 or ApoE3. In MS, people with ApoE4 genes also have a more severe course and an earlier onset of MS.
Now you can see here from this cartoon of the ApoE3 and ApoE4 proteins, that their structures are quite different. ApoE4 has the end of the protein that sticks out from the major backbone. It is now possible to conceive of developing a drug that will bind that renegade tail of ApoE4 and push it back to the framework of the molecule, so that it resembles ApoE3. This approach could potentially provide an outstanding opportunity to develop drugs that not only change the shape of ApoE4, but also modify the course of MS.
I hope it’s now becoming quite clear where this work is headed. Our first step will be to identify the location of MS genes in great detail. There are probably 70 genes contained in each region that have thus far been identified. Once the genes are identified, their protein has to be deciphered and the function of the protein determined. Armed with this knowledge, it should be possible for the first time in our history, to develop a therapy designed to correct the protein abnormality that’s associated with MS. We may also be able to think about primary prevention--identifying and treating MS before it occurs. And finally, perhaps, these genetic studies will be valuable in helping us to diagnose MS and also the form or course that MS might take.
This work could never have happened without the support and encouragement of the National MS society—through grants to support MS genetics research and funding to support salaries of bright young people who are committed to MS research. In this group alone, from just one university, three scientists have received junior faculty awards and nine fellowship grants. This funding has facilitated our development as physician scientists, has made it possible for us to pursue MS research, and has certainly institutionalized our university’s commitment to MS.
Moderator: The role of gender in multiple sclerosis has piqued the curiosity of clinicians and scientists for decades. It is widely known that women are twice as likely to develop MS as men. We also know that disease activity slows during the last trimester of pregnancy when certain pregnancy hormones are at their highest levels and is likely to increase in the months following delivery as these hormones resume previous levels. Because of observations such as these and the potential role for sex hormones in the treatment of MS, that the National MS Society has targeted gender differences as an important area of study.
Dr. Rhonda Voskuhl is assistant professor of neurology at the University of California at Los Angeles and she will now share with us her expertise in the area of gender and MS. Dr. Voskuhl: There are two clinical observations that are extremely important in multiple sclerosis. One is that women are protected transiently during late pregnancy and secondly is that young men are less susceptible than young women to develop MS. I would like to talk about each of these clinical observations and show how we’ve gone into the animal model to try to dissect the mechanism for them and then go on to design pilot clinical trials to see if novel therapies can be created from these clinical observations.
To proceed with the first observation, women are protected transiently during late pregnancy. This means that there’s a significant decrease in relapse rates during the third trimester and that there’s an increase in relapse rates postpartum. To try to figure out what might cause this change in disease activity or this protection during late pregnancy, we focused on sex hormones. It has been known for quite some time that sex hormones are at low levels during the initial stages of pregnancy, increase progressively during pregnancy to reach their highest levels in the third trimester, then drop precipitously postpartum. The specific hormones we focused on were progesterone and estriol—estriol being the primary estrogen of pregnancy. The way that we ascertained whether these hormones were protective was to use the animal model experimental autoimmune encephalomyelitis, or EAE.
Mice were immunized with a myelin protein, living cells were taken out and then transferred into another set of mice that had either been treated with the estriol, with progesterone, or with a placebo. Then the subsequent clinical course of EAE was compared between the groups to see if there was a treatment effect. We found, as expected, that the placebo treated mice were severely affected with EAE, having grade 4 disease severity. Grade 4 means that they were completely paralyzed in at least one of their legs. In contrast, the mice treated with the estriol at either the 5 milligram or the 15 milligram dose, had a significantly decreased severity of disease, with the peak of disease being only a grade 2. Grade 2 means they had only postural instability, with no partial or complete paralysis. Incidentally, the progesterone treated mice were very similar to the placebo treated mice. So progesterone had no effect, but estriol clearly made the disease better.
The next thing we did was to determine whether the estriol dose we had given would induce a level of estriol in the blood that was similar to the level attained in normal pregnancy. So we took the blood from mice that were either pregnant or not pregnant and compare the levels of estriol in their blood with those that were taken from mice that had received the estriol treatment at 5 or 15 milligrams. We found that the estriol level in the serum or blood of mice that were treated with the 5 milligram dose was very similar to what was observed in the blood of mice that were naturally pregnant. This was exciting because it meant that we could induce a level of estriol in the blood of patients that was very similar to what occurs naturally during late pregnancy, and very likely see a decrease in the disease severity or activity. This was also exciting because we knew that Estriol had been given previously to a number of women for hormone replacement therapy and had been extremely well tolerated.
So we proceeded with the design of a pilot clinical trial in MS patients using oral estriol. The patients were either relapsing- remitting or secondary-progressive. They were female, age 18 to 50. They had to either have refused or been unsuccessful with the ABC drugs. They could not be pregnant, on oral contraceptives, or have endometrial or breast cancer. The design of the trial involved a pre-treatment period, a treatment period, a post-treatment period, and then a re-treatment period. The pre-treatment period involved a 6-month time period in which MRIs were done every monthto determine the level of disease activity that each patient had. Then the patients went into the six-month treatment period, during which they received 8 milligrams of estriol per day, and MRIs every month. Then the patients went off estriol and entered the six-month post-treatment period. MRIs were again done every month.
And finally, in a four-month re-treatment phase of the study, we again treated patients with estriol and added progesterone to protect the endometrium. We also saw the patients in the clinic every three months and did other cognitive and immunological studies.
As expected, the treatment was very well tolerated, with minor menstrual cycle abnormalities. One patient had a uterine fibroid that enlarged transiently and then decreased when she went off the drug. There was no evidence of breast cancer, endometrial hypoplasia and no laboratory abnormalities. We checked serum or blood levels of estriol during the trial and found, as expected, that they were undetectable or at the limits of detection in the pre-treatment period. They were increased during treatment, then decreased during the post-treatment period, and then increased again during the estriol re-treatment period. Interestingly, as you see on the right, we compared the estriol levels in these patients to estriol levels in pregnant individuals. These are normal individuals who are pregnant and are not on estriol. As you can see, the levels obtained during the treatment period in the patients were very similar to levels observed in the pregnant patients during the six-month pregnancy period. The pregnancy periods that you see are divided into six months on the left and eight-and-a-half months on the right. So again, what we observed when we gave 8 milligrams of estriol to these patients, was that we induced a serum level of estriol that was very similar to what occurred naturally during six months of pregnancy.
Importantly, we looked at the MRI as an indicator of possible efficacy. The level of gadolinium enhancing disease activity— both volume and number of enhancing lesions—was compared between the different treatment periods. We saw an effect in the relapsing-remitting, but not the secondary-progressive patients. Specifically, what we observed in the relapsing-remitting patients was the following: At the baseline, we had a pre-treatment period that included months one 1 through 6; at the initial phase of the treatment period—months 7 through 9, we saw a decrease in the enhancement or the lesion activity; at a later time point during the estriol treatment period--months 10through 12, this decrease in disease activity continued, becoming even a little bit more significant because there was less variability.
Then, interestingly, when the patients went into the post-treatment period--months 13 through 15, we began to observe variability. This meant that some of the disease activity was coming back in some patients, but not others. Later in the post-treatment period, at months 16 through 18, the disease activity returned to baseline. And last but not least, when we went into the estriol re-treatment period, during months 19 through 22, we again saw a reduction in the disease activity. So to summarize these results: There is no evidence of toxicity. There was a hint of efficacy. And there was sufficient evidence to justify further study of estriol in relapsing-remitting MS.
Now to move onto the second part, which related to the clinical observation that young men are less susceptible to MS than young women. Why might this occur? Well, it could be due to differences in sex hormones, differences in sex chromosomes, or both. With regard to sex hormones, it could be that male sex hormones are protective, female sex hormones are deleterious or both. To discern between these possibilities, we undertook EAE experiments again, comparing mice that were either castrated to remove hormones or not castrated, and then compared the disease course between the two groups.
What we found in these experiments was that castration of male mice made the disease worse. This meant that testosterone was likely to be protective. We found that castration or ovariectomy of female mice had no effect on the disease. This meant that female sex hormones such as estrodial and progesterone, which exist at low levels that fluctuate during the menstrual cycle, probably don’t have a significant effect on the disease.
So to determine whether male sex hormones are protective, we proceeded with another experiment and that was to treat mice with either testosterone or placebo to see if the disease course was affected. Indeed, what we found was that the testosterone treatment was protective in female mice as compared to placebo.
We considered giving testosterone treatment to female MS patients, but when we considered the fact that they might get hirsutism, or masculinization, we felt like it wouldn’t be of widespread use because of the high doses that would be necessary. We then began to consider however, what might happen if we gave men supplemental testosterone. So we did the next experiment to determine whether supplemental testosterone treatment might be protective in young, healthy, male mice that had not been castrated.
We found that supplemental testosterone was protective in male mice as compared to placebo. This became the basis for a clinical trial in which we want to give supplemental testosterone to men with MS, the idea being that, even at supplemental levels, it could still be protective.
Thus, these observations in EAE mice make a lot of sense when one thinks about MS. For example, it’s known that testosterone begins to decline at the age of 30, at about 1 to 2 percent per year. It’s also known that when MS starts in men, it generally occurs at a relatively older age, around 30 to 40 years of age. So the hypothesis is that the reason men don’t get MS like women do when they are about 18 to 20 is because they have very high testosterone levels that are protective.
And finally, based on these results, we have now designed a preliminary trial to test testosterone in men with MS. In summary, there are two hormonal situations that are protective—either to be a young male and have high testosterone levels, or to be a pregnant female and have high Estriol levels.
Moderator: For many years people with MS have used various types of therapies beyond the boundaries of conventional medicine to treat their disease. For today’s discussion the term CAM (C.A.M.) will refer to complementary and alternative medicine. The common use of CAM among people with MS makes it very important for all of us to learn more about the potential benefits and risks associated with these interventions. Each type of therapy needs to be evaluated individually. Some therapies may be beneficial; others may turn out to be useless or even harmful for people with MS. The challenge lies in finding effective ways to evaluate the various types of interventions that make up CAM. Tonight, Dr. Allen Bowling will discuss the efforts to integrate beneficial CAM therapies with conventional medicine, as well as the research behind the safety and efficacy of different therapies. Dr. Bowling, Clinical Assistant Professor of Neurology at Colorado Health Sciences Center and Director of the CAM program at the Rocky Mountain MS Center, is the author of Alternative Medicine and Multiple Sclerosis.
Dr. Bowling: In this program today, I’m going to talk about alternative medicine and Multiple Sclerosis. Although the use of alternative medicine is quite common, the subject of alternative medicine is often not included in MS education programs. In fact, up until recently, the whole area of alternative medicine was viewed kind of like the big elephant in the living room no one was paying attention to. I think it’s commendable that alternative medicine is being included in this education program today. As you’ll learn through the course of this program, alternative medicine and MS is currently an exciting area in which there are many active research programs. Before talking about specific therapies, I’d like to define some of the terms.
First of all, alternative or unconventional medicine typically refers to medical therapies that are not generally available at community hospitals or taught in medical schools. This definition is a bit of a moving target because some medical schools now offer programs in alternative medicines. Other terms that are sometimes used include complementary and alternative medicine or the shortened version, CAM. Complementary medicine means that unconventional therapies are used alongside conventional medicine. Alternative medicine means that these therapies are used instead of conventional medicine. As you start thinking about various alternative therapies, you realize that this is a huge topic. It includes acupuncture, diet, dietary supplements, homeopathy, a whole range of therapies.
To provide a focus today I’m going to discuss alternative therapies in which there has been recent research related to MS. There have actually been some recent research studies looking at the use of alternative medicine among people with MS. These studies have been done in the United States, Canada, Australia and Europe. In these studies, it appears that about one-half to two-thirds of people with MS use some form of alternative medicine. In other words, the majority of people with MS appear to use some form of alternative medicine. People with MS also appear to use the unconventional medical therapies alongside conventional medical therapies. In other words, they use them in a complementary manner.
There are some obstacles associated with doing research in alternative medicine. When clinical trials are done to determine whether a medication is effective, there typically are two research groups. There’s one research group that receives the active form of the medication and another group that receives an inactive form or a placebo. During the course of the clinical trial, the two groups are monitored to determine if the group that received the active medication receives significant benefit. In the area of alternative medicine it is sometimes hard to develop a placebo treatment. With acupuncture, for example, you can imagine the difficulties associated with trying to determine how to insert needles, but not have it be genuine acupuncture. Also, clinical trials are often blinded, meaning that the investigator and the patient do not know who is receiving active treatment and who is receiving the placebo. Blinding can be difficult to achieve with some forms of alternative therapies.
Another obstacle in alternative medicine research is funding. For conventional medications, there’s a profit that can be made through patenting drugs that are found to be effective. That financial drive and those resources are not generally available for alternative therapies because these therapies generally cannot be patented. There is also limited interest among researchers in alterative therapies. Part of this is due to a lack of familiarity with these therapeutic techniques. Also, there is not a clear scientific rationale for some of the alternative therapies that are currently practiced.
Now, I’d like to talk about specific alternative therapies. The first type of therapies I’m going to talk about are herbal therapies. One herb that many people might have heard of is gingko biloba, an extract from the leaf of the gingko biloba tree. This extract contains several interesting compounds, some of which, in theory, may be beneficial for MS. Based on this theoretical evidence, there were some studies done in the 1990s treating people with MS attacks with gingko biloba. In these studies, it was found that gingko biloba is not effective. Gingko has also been studied in people with presumed Alzheimer’s disease and it may provide a benefit in that area. Based on those studies, some recent studies started looking at the effects of gingko on MS associated cognitive difficulties. These studies are currently underway at the University of California, San Diego. If gingko is taken, it should be kept in mind that it may increase bleeding and therefore should be avoided by people who take blood-thinning medications, or people who have bleeding disorders. In addition, gingko may increase the risk of seizures.
Another herb that has a long and colorful history in relation to MS is marijuana. Like gingko, marijuana contains chemicals that in theory could be helpful for MS. These chemicals include THC or tetrahydrocannabinol and related chemicals. There are limited clinical studies suggesting that marijuana could be helpful for MS related muscle stiffness or spasticity, however, no large formal clinical study has yet been reported. With marijuana, it’s important to keep in mind that marijuana smoke, like tobacco smoke, contains cancer-causing chemicals. As a result, there are significant risks associated with smoking marijuana on a regular basis. There is currently research being done to try to develop safer ways to administer marijuana. In addition, there are large, formal clinical studies currently being done in England and in California, looking at the effects of marijuana on various MS-related symptoms, including pain and spasticity.
Vitamin D has a possible relevance to Multiple Sclerosis. As most people know, Vitamin D and calcium work together to maintain the density and strength of bone tissue. There is a decrease in bone tissue referred to as osteoporosis. Recent evidence suggests that people with MS may be at increased risk for developing osteoporosis. There are some risk factors for osteoporosis that overlap with some of the features of the people with MS, including being female, not walking as much as you would otherwise, decreased sunlight exposure, use of steroid type medications. So this is an important area of study and osteoporosis may, in fact, be under diagnosed and under treated in people with MS. Another interesting aspect of Vitamin D is that it mildly suppresses the immune system and therefore could potentially be helpful for people with MS. There are currently studies underway in New York and Pennsylvania to evaluate the clinical effects of Vitamin D in people with MS, and several of these studies are funded by the National MS Society.
Another form of alternative medicine that’s familiar to many people is acupuncture—a component of traditional Chinese medicine. There are some studies that indicate that acupuncture may be helpful for some types of pain and nausea. There are surprisingly few studies that have been done looking at acupuncture on people with MS. There was a recent survey done in British Columbia, of people who had used acupuncture for MS. About two-thirds of the people reported beneficial effects for a variety of symptoms. This was not a formal clinical trial, so the results and the meaning of the results were not entirely clear. To provide a clearer view of acupuncture in MS, clinical studies are currently underway. One study in British Columbia is looking at the effects of acupuncture on MS-associated bladder difficulties, and a study in Oregon is looking at the effects of acupuncture and Chinese herbs on MS-related fatigue.
Another area that is sometimes is included in alternative medicine is exercise. It could be argued whether exercise is medicine, or whether it’s conventional or unconventional. I’m going to talk about it today because I think exercise can provide significant benefits for many people with MS.
In the 1990s, there were studies done that showed that exercise can provide some obvious physical benefits like increased strength or increased walking ability. Exercise can also provide emotional benefits. It may decrease depression, improve anxiety and decrease anger. One of the most paradoxical effects of exercise is that it may actually decrease MS-related fatigue. Conventional exercise programs can be developed by working with a physical therapist.
There are some unconventional forms of exercise. One is Tai Chi. Many people are familiar with the slow body movements in Tai Chi. Tai Chi is a component of traditional Chinese medicine that was developed hundreds of years ago. There has been one study of Tai Chi in people with MS. This study indicated that Tai Chi may decrease muscle stiffness and increase walking steadiness. Further formal studies are needed about Tai Chi in MS. Many people with MS also report benefits with yoga, but there have not been any large published clinical studies to date.
At the Rocky Mountain MS Center, we have a program on complementary and alternative medicine. One important aspect of this program is to provide user-friendly information to people with MS. One way that we do this is through a Web site. The Web site address is MS-CAM.org. On this Web site, we provide MS-relevant alternative medicine. In addition, we have an email-based survey system in which we learn about people’s experiences with various alternative therapies. We then provide the summary of the survey results on the Web site. Through this process, we are able to provide people with MS information about alternative medicine. In addition, through the participation of the users of the site, we’re able to develop new MS-relevant alternative medicine information.
Through this program, I hope it’s become clear that it’s not reasonable to have a totally positive or a totally negative view of alternative medicine. Each alternative medicine therapy needs to be interpreted within the context of MS. When that’s done, it’s clear that some therapies are promising. Other therapies appear to be dangerous or not effective, and nearly all therapies require further study.
Questions & Answers:
Moderator: Well these three MS experts have offered a wealth of information that I am sure has suggested many questions to our viewers. Now that they have joined me here in the studio, let’s move into the live question and answer segment.
Question: I’m a 48-year-old man and I’ve had MS for 10 years. Should I begin to take testosterone now and will that make my symptoms better?”
Dr. Voskuhl: Well that’s a good question. I think one of the main things to be addressed would be what type of MS do you have? For example, the ABC drugs have been shown to be effective in relapsing-remitting MS, but it remains to be determined whether they’re effective in secondary-progressive or primary-progressive MS. Our trial with testosterone, since it is thought to be anti-inflammatory, will focus primarily on relapsing-remitting MS.
And so if you have relapsing-remitting, you may be a candidate, but again, I would wait until we finish the studies that we need to do to prove whether it would be effective.
Question: My wife and I want to start a family, but we’re scared about her MS. Is there any way to test and find out if the baby has it or is going to get it?
Dr. Hauser: In general, the risks for your baby or babies will be very low, less than 5 percent. It’s worth remembering that 4 out of 5 people with MS belong to families in which they’re the only affected member. So we’ve generally advised people not to make reproductive decisions based upon the fear that your children might be at slightly increased risk for MS. The only exception to this advice might be for people who belong to those families in which many people, perhaps 4 or more family members, are known to have MS. But this really represents a very small number of families in America.
Moderator: Dr. Hauser, you mentioned a slightly increased risk. What sort of number are we talking about in terms of a percentage increase?
Dr. Hauser: Well, one thing that we’ve learned is that the risk may be a little bit different in different families, but the risk is perhaps one in 20 at the most for most people with MS.
Question: Are there any studies that demonstrate a genetic link for autoimmune diseases in general? This person has MS and her 7- year-old son was recently diagnosed with diabetes and they would like to know if there’s any relation.
Dr. Hauser: That’s a very interesting question. In fact, just two weeks ago, there was a study from the Sardinian region of Italy showing that there was a relationship in that Italian population between diabetes and MS. What has become increasingly apparent is that some families seem to be at slightly increased risk for multiple autoimmune diseases, including MS. But exactly how important this is for most people with MS is the subject of study, and we’re not yet certain.
Question: My friends keep telling me about all the benefits of using hyperbaric oxygen chambers to treat MS. I know a woman that swears this has made her MS better, but the closest treatment center to me is more than two hours away. Should I go? I’ve had relapsing remitting MS for more than 10 years.
Dr. Bowling: It’s a very timely question. I’m from Colorado also and hyperbaric oxygen has been advertised and has actually increased in popularity here in the last year or two. Hyperbaric oxygen therapy involves being placed in a chamber with a high oxygen content to increase the amount of oxygen in the blood. This type of treatment is helpful for diving sickness and poorly healing wounds. In terms of MS, there was a study that was reported in 1983 showing that it was helpful for MS, but it’s very important to know that there were 7 studies afterwards that showed it was not effective. So the conclusions from this are: that the first study did not give us a true finding; that the seven subsequent studies show more reliable information; and that hyperbaric oxygen is not an effective therapy for MS.
Moderator: I’m curious, Dr. Bowling, can you say briefly what the general theory is as to why that approach might help?
Dr. Bowling: The idea relates back to an older idea about MS that it was related to a lack of blood flow. Since hyperbaric oxygen increases the oxygen in the blood, the idea was that it would increase the amount of oxygen that was being delivered to the brain tissue. However this is no longer how we think the disease process occurs in MS.
Question: Will you please comment on the effect of the postpartum period on MS. Is there any link with the hormonal changes of the postpartum period and MS?
Dr. Voskuhl: Yes, the postpartum period is a very important time. It has been known for quite some time that while MS relapse rates are clearly decreased late in pregnancy—in the last trimester— there is a period of about six months after the baby is delivered when patients are actually at increased risk for relapses. This may or may not be due to hormonal fluctuations. It would be important to identify what it is due to, because if we knew that, then we could modify that hormonal fluctuation and possibly prevent the postpartum exacerbations.
Question: What benefits have been found in vitamins— specifically evening primrose oil and cod liver oil?
Dr. Bowling: Your question taps into a whole area that was researched quite extensively about 20 years ago relating to the possible connection between polyunsaturated fatty acids and MS. Now the polyunsaturated fatty acids include omega 6 fatty acids like you’d find in evening primrose oil. They also include omega 3 fatty acids, which are the fish oils that you would find in cod liver oil. There’s some scientific evidence that those polyunsaturated fatty acids mildly suppress the immune system, so there are some theoretical reasons why they might be helpful. The omega 6 polyunsaturated fatty acids decrease the severity of an MS- like disease in animals known as EAE. There were actually three clinical studies done approximately 20 years ago with omega 6 fatty acid supplementation, and two out of those three studies showed some mildly positive effects. So at this point, the results are not definitive, but there are some suggestive results with the omega 6 fatty acids. At the recent neurology meetings that were held here in Denver about a month ago, there were some preliminary positive results with omega 3 fatty acid supplementation. So there’s some rationale for that kind of approach.
I wouldn’t do those types of therapies instead of the conventional ABCR type [Avonex®, Betaseron®, Copaxone®, Rebif®] medications, but if something was to be done in addition to those, that might be an area that would be worth considering. Question: If you were on methotrexate, are there certain herbs or vitamins you should or should not take?
Dr. Bowling: Well with methotrexate, there are very limited herbal interactions. There are some herbs that contain salicylates. Salicylates are aspirin-like compounds and those herbs can actually interact with the methotrexate. So that would be something to check on. There’s willow bark that contains salicalate. There are two or three other herbs that are not used very frequently that can interact with methotrexate.
Question: I understand that people who have a close relative with MS have a greater chance of developing the disease, but how common is it for a family to have several people with MS?
Dr. Hauser: Well, this is uncommon but not rare. There are families across America that have two, three, four, or even as many as nine people who are affected with MS. Families like these can be of great value to the research community because they help us to understand, in a much easier fashion, where the genes are that might contribute to a family’s special risk.
Question: How do you explain disease severity differences in identical twins, one of whom has mild relapsing remitting MS and the other who has severe primary progressive MS and neither has been on any of the ABCR drugs?
Dr. Hauser: That really is a very important question. It highlights to us that genetics is only a small piece of the puzzle and I would say that not only is it common for identical twins to have very different courses of MS, but the majority of identical twins sets in which one member has MS have a second twin member who is free of MS. So, much like the teddy bears I mentioned before, that were different because of environmental differences, I think genetics is only a part of the problem in MS. It sets the stage for a complicated environmental series of interactions across one’s life that determines whether or not this genetic predisposition plays itself out.
Question: In addition to having MS, I have been diagnosed with osteoporosis at the age of 47. Hormone replacement therapy has been suggested as a plan of care. Have there been any studies or do you have any suggestions on the use of HRT with MS?
Dr. Voskuhl: Yes, this is a commonly asked question and I think it goes back to the issue of a person’s natural circulating levels of estrogen during the menstrual cycle; do they or do they not play a significant role in MS? In the animal models of MS, some groups have reported that ovariectomy or removing estrogens makes the disease worse. Others, such as our group, have not shown that to be the case. While we know that high levels of estrogen during pregnancy are protective, it’s really not clear whether low fluctuating levels during the menstrual cycle play any role at all.
Now, there is one anecdotal study in MS patients who basically went through menopause and they filled out questionnaires retrospectively, and they describe that their MS was better. Unfortunately, there were no MRI data showing level of disease activity, to indicate whether it was merely a subjective appraisal of improvement, or whether the hormonal replacement therapy actually helped them. Clearly, the decision to take HRT should be made with the woman and her gynecologist, and that should be the first priority. Personally, I think that it wouldn’t hurt anything, but I wonder if the estrogen dose will be of the right type or of a sufficient level to do much good.
Question: You know we always talk about the fact that MS is not directly inherited. We’re also hearing about genetic predisposition and we want a clarification on the terms hereditary and genetic predisposition and the differences between the two.
Dr. Hauser: Well this is often a difficult question to answer because we don’t know for certain the exact number of genes and how these genes are working together with the environment, to make some people more susceptible than others. MS is not like Tay-Sachs disease—a disease in which there is a specific single gene and any person who inherits that gene from both parents develops the disease. MS is like all of the other common important medical diseases of human kind—cancer, heart disease, other autoimmune or inflammatory diseases. We know that the disease tends to run in certain families, but each individual in these families is generally at a very low risk for the disease. So in a simple sense, predisposition means that there is a somewhat increased risk in members of certain families. Every family has a disease or several diseases to which their family seems to be slightly predisposed. But this is quite different from a very strong genetic effect as one has in some single gene diseases that strike the nervous system.
Moderator: And just because there is a predisposition within a given family, we don’t know that that’s necessarily genetic, right? I mean it could be because of the diet.
Dr. Hauser: That’s correct. Not all predisposition is genetic. Some predisposition is due to sharing an environment that’s similar.
Question: First I read St. John’s Wort was great for depression, that it was being prescribed by doctor’s all over Europe, and then I read that studies in this country found it wasn’t very good at all. So how do you know whom to believe?”
Dr. Bowling: That’s a very confusing story and it’s kind of an evolving story about St. John’s Wort. As you mentioned, there were many studies conducted, mainly in Germany, showing that it appeared St. John’s Wort had an anti-depressant effect on people with mild to moderate depression. There was a study done in the United States a couple of years ago that found that St. John’s Wort was not effective for moderate to severe depression. There was a more recent study showing that it was not effective for people with moderate depression. That study’s a little difficult to interpret because the anti-depressant drug, Zoloft®, that was used in that study, was also not found to be effective relative to placebo.
There’s still a question as to whether St. John’s Wort is effective in people with mild depression or mild to moderate depression. Also, in relation to St. John’s Wort, it’s been increasingly recognized that it can have important interactions with other medications. St. John’s Wort affects the liver in a way that it can decrease the effect of other medications including the birth control pill. Actually the joke that’s going around now is that there probably are quite a few little St. John’s who are running around now because of that interaction between St. John’s Wort and the birth control pill. So with St. John’s Wort, which is an an herb, it’s very important to talk with your physician or other healthcare professional —first about the herb itself, and then also about diagnosing and treating depression. That’s not something that you want to be doing on your own.
Moderator: Dr. Bowling, in general, are we getting more clinical studies involving these herbal treatments—like St. John’s wort and Echinacea, whatever they happen to be? Are we getting more definitive scientific evidence on these things?
Dr. Bowling: Yes, there are more and more definitive studies, and there are more formal, rigorous clinical trials being done. A lot of the past studies have not been formal, controlled clinical trials. We’re getting more rigorous information. A lot of this is happening through the National Institutes of Health (NIH), through their alternative medicine program. The National MS Society has also been providing more funding for alternative medicine research programs.
Question: I was wondering if someone could talk about the current status of stem cell research.
Dr. Hauser: Well this is a very exciting area in biology and it’s hard for a week to pass without reading about stem cell research on the front page of one of our local newspapers. Stem cells are cells in the body that are able to mature into a variety of other cells. And in our case, we’re interested in cells that can mature into cells that make myelin and perhaps could help to remyelinate thenervous system after there has been demyelination from MS. Stem cells have now been found in both embryos and in adults.
Adult stem cells have been an area of great interest. Could we figure out what the chemical signals are that could turn a stem cell in our blood or in our bone marrow, or even in our skin, into a myelin-producing cell? There are trials now, tentative early trials underway both in America and in Europe, that are beginning to explore stem cell transplants for people with MS. While most of us are very excited about stem cells, I think that we’re even more excited by the idea that cells that are capable of maturing into myelin producing cells may also be present in MS lesions in a slightly more mature state. So they’re not stem cells, but they’re not myelin-producing cells either. If we could understand the chemical signals that turn an immature cell into a myelin-producing cell, perhaps we would then have a new kind of therapy for people with MS, where a drug could be given that could mature an immature myelin-producing cell right in an MS lesion.
Question: Can you explain the relationship between MS and EAE? I know that they study animals with EAE but is that the same as MS and do people also get EAE?
Dr. Voskuhl: EAE is the most widely used animal model for Multiple Sclerosis. It really can’t be lumped into one category because interestingly enough, with the different genetic backgrounds of the mice that get EAE, you actually have different EAE-type disease courses. So, for example, in some mice you’ll get a relapsing-remitting disease. In other mice, you will get more of a chronic progressive disease, and in yet another strain of genetically distinct mice, you might get a one-time monophasic type of disease.
So as it turns out, EAE is actually a quite useful model to answer various questions about MS. For example, if you wanted to study what causes remissions in MS, you want to use the remitting model. If you wanted to study what makes it progressive, you want to use the progressive model. Interestingly, it’s different than MS most dramatically in the sense that it is experimentally induced, and so you have to immunize a mouse with a myelin protein and bring up these white blood cells specific for the myelin protein. In MS, however, it occurs spontaneously. Due to the genetics and environmental influences these cells are in essence sensitized to self, whereas experimentally that has to be induced in EAE.
Question: All of the new treatments seem to be for relapsing remitting MS. I have the primary-progressive kind and my doctor says there isn’t anything for me yet. What makes my kind of MS so different?”
Dr. Voskuhl: Well as clinicians, we’ve known for quite some time that the course of primary-progressive MS seems to be quite distinct from that of relapsing-remitting and secondary-progressive MS. Most of us see the relapsing-remitting and secondary-progressive MS as a continuum. You’ve got the early relapsing-remitting phase that often goes gradually over the years into the secondary-progressive phase. Primary-progressive MS seems to be quite distinct. It actually occurs in males more often than in females, whereas the opposite is the case with the relapsing-remitting and secondary-progressive forms. It also takes a course that can primarily affect the spinal cord as opposed to the brain, and can be very unrelenting in its course. So that clinical data, in addition to other data based on the difference in the immunology of the two diseases, the genetics of the two diseases, and even the pathology of the two diseases, make it seem to be a very different entity from the relapsing-remaining or secondary-progressive MS. Currently the ABCR drugs are, or probably will all be tried, in primary-progressive MS and the jury’s still out whether they will be effective.
Question: How does diet affect the disease?
Dr. Hauser: That’s an excellent question. That relates back to the earlier question of the evening primrose oil and the various fish oils. There are limited studies and these were done about 20 years ago, suggesting that decreasing saturated fat, and increasing polyunsaturated fat may have a mildly beneficial effect, but those results are not definitive. The idea is that of all the fats, the polyunsaturated fats, which are like omega 6 fatty acids and omega 3 fatty acids, mildly suppress the immune system. Because immune system activity is generally too high in MS, there is some rationale for that type of approach.
Moderator: Most of the neurologists I’ve spoken with in the past about the issue of diet, sort of generalized the answer by saying, “Well, if you’re healthier, you will deal better with anything that you’re dealing with, that a healthy body makes for a healthier person regardless of the MS or anything else.” Is that sort of your approach, or do you try to find certain foods that should be taken or shouldn’t be taken?
Dr. Hauser: If someone wants to take this kind of approach, there are some dietary changes that can be made to balance the diet. Obviously a well-balanced diet, no matter what the particular constituents, is going to be healthier for someone than a diet that’s not balanced. But there’s a way to have a well-balanced diet in a way where the saturated fats, like red meats, are de-emphasized, and polyunsaturated fats are relatively increased. To make that kind of change, you can meet with a dietician. There is an older approach that is quite extreme, referred to as the Swank diet. That has a real severe decrease in the saturated fat and some accentuation of the polyunsaturated fat in the diet. Unfortunately, the studies that were done with the Swank diet were not controlled.
In other words, it was not a placebo treated group, so it’s very difficult to interpret that information. If you do make those kinds of dietary changes, it’s actually quite important to supplement the diet with Vitamin E. And sometimes in books, it’s suggested that if you’re doing this approach, you should be taking thousands of units of Vitamin E. In fact, you just need fairly low doses, probably 100 to 400 units daily, but if you increase the polyunsaturated fats, that puts you at risk for developing Vitamin E deficiency. That’s the reason to supplement with moderate doses.
Question: I believe there’s a study underway on the effects of estrogen replacement therapy for postmenopausal women with MS. Are there any preliminary results available at this time?
Dr. Voskuhl: I’m not aware of the results of that study as yet. I think it’s good that it’s being done, of course, and one would hope that as compared to a previous study with hormonal replacement therapy in menopause and MS, they would have very strict disease markers—for example, MRIs in addition to clinical exams in order to document whether the hormonal replacement therapy is actually affecting the disease activity itself. But I look forward to those results, and it’s possible that they may be very promising. Again, it will depend on the amount of the estrogen used in the hormonal replacement therapy, the type of estrogen used. But it would be promising to hear the results of that.
We always have to emphasize that all preliminary trials have to be followed up with phase 2 trials and phase 3 trials, so it takes minimally a year and sometimes up to a decade or more to prove that in fact it’s really beneficial as compared to placebo for example.
Question: How much more likely is it that children or grandchildren will have MS if their mother does than if the father does?
Dr. Hauser: Well, there was one study that suggested that fathers tend to pass MS onto their sons much less often than to their daughters or that mothers pass to sons or daughters. But in more recent studies, this finding hasn’t been consistently reproduced. One of the things that we’ve learned about inheritance of MS is that there may be some differences between different people and families. Dr. Voskuhl spoke earlier about the possibility that primary progressive MS may be a little bit different. It’s also possible that what we call relapsing- remitting or even secondary-progressive MS, may not be the same or exactly the same problem in different families. But if we take all people with MS together, the risk that a mother will pass MS on to children or grandchildren is about the same as the risk that the father would.
Question: Are there any other therapies, alternative or otherwise-- besides marijuana—available to help MS patients who have uncontrollable spasticity?
Dr. Bowling: You have a whole variety of conventional medications that are available and I would actually, if you have severe spasticity, think first of a conventional medical approach. Mild spasticity might be a symptom in which some unconventional approaches would be reasonable. In terms of conventional approaches, there are drugs such as baclofen (Lioresal®)or tizanidine (Zanaflex®). Clonazepam (Klonopin®) can also be helpful. For more severe forms of spasticity, there’s a drug that’s been in the news a lot recently, botulinum toxin (Botox®), which can actually be injected into the muscles that are stiff. Also for people with more severe forms of spasticity, a pump can be inserted that delivers baclofen at the base of the spine, and that can be very effective for relieving spasticity.
And you mentioned marijuana. There’s limited evidence there. The concern with marijuana is the health risks that are associated with it that I mentioned before. For people who have milder forms of spasticity, a massage is sometimes reported to be helpful, although surprisingly there aren’t any studies that have been done with that. Another approach for milder forms that can be very helpful is a good exercise program, especially one that emphasizes stretching. That can be developed in conjunction with a physical therapist. There also are unconventional forms of exercise like Tai Chi and yoga. There was a limited study with Tai Chi and there was some evidence that it may have relieved some muscle spasticity. There actually has not been a study done yet with yoga, but many people with MS who do yoga, report that’s one of the benefits they get from it.
Question: What are the major side effects of estriol therapy? I’m 59 years old with secondary progressive MS and not on any of the ABC drugs.”
Dr. Voskuhl: Okay, first of all, I want to emphasize that when we gave estriol in our pilot trial, we actually found that it was effective in the relapsing-remitting group but not in the secondary-progressive group. Now this may have been because we need larger studies to find an effect. It is yet to be determined whether it would be effective in secondary progressive. To get to the first part of the question and that is, “what would be the side effects”?
What we did in our trial, and what I would recommend is anyone who is going to take estrogen or estriol, is to get a screening mammogram to make sure they don’t have breast cancer. The risks of estriol are similar to any other estrogen although somewhat less because estriol is a very weak estrogen—weaker even than the conventional birth control bills that women take. So the risk of inducing endometrial or uterine cancer or breast cancer is very small-- Regardless, I think it’s still wise to make sure that women don’t have breast, uterine or endometrial cancer before they start taking estriol. And in addition, if estriol is to be given for longer than six months, one would definitely want to take progesterone with it because that protects the endometrium from hypoplasia and subsequent cancer. So again, estriol should be given only after it’s been proven to be effective—which we are still working on. And when it’s given, it should be under the supervision of a gynecologist.
Question: My family wants me to go in for bee stings. It sounds from everything that I’ve read that this therapy works really well for people with MS. Is there any research on this?
Dr. Bowling: There’s very limited information about bee sting therapy. This was actually initially claimed to be effective for arthritis. More recently it’s been claimed to be effective for MS. With MS, in limited studies in EAE, the animal model of MS that we’ve been talking about, bee sting therapy appeared to have no effect or actually may have mildly worsened the disease process. At Georgetown University, Dr. Richert and Dr. Bellanti have completed a phase 1 study where they’ve looked at the safety of bee sting therapy. In those studies, apparently, the treatment did appear to be effective although the results have not yet been published. If this does indeed turn out to be the case, then the next step would be to do a larger phase 2 study looking at the efficacy and safety of the therapy For the moment, however, we have only limited information in animals.
Question: Dr. Hauser, you mentioned earlier that only 50 percent of people with MS have a gene that may relate to the efficacy of Copaxone. Is it possible to have a genetic test to see if you fall into that group that would be more successful taking Copaxone?” Dr. Hauser: Yes, there may be genes or immune differences between people that relate to the efficacy of all of the injectable therapies that we have for MS. This is an area called pharmacogenomics. Unfortunately, the information at this time is just not available in a way that is helpful to people in making decisions about which injectable therapy to consider for their condition. I think that all of us believe that the decision to stop or change any one of these medicines should be determined by the symptoms and signs that you have while on the medicine. This is a decision that you and your doctor should make together about whether or not you’re responding to the medicine or if another should be tried.
Question: What studies have been done when a woman is in her premenstrual phase with the hormonal changes. Does that seem to make the MS worsen?
Dr. Voskuhl: This is an excellent question too. It relates to the fluctuating levels of estrodial that occur during the menstrual cycle. And there is some evidence that many women have a worsening of their MS symptoms right before their period. Now, I want to point out that that is a little bit different than having relapses prior to their menstrual period. So what patients will say is that my pre-existing signs or symptoms seem to worsen a little bit right before my period. So this to me indicates that it’s very possible that hormones may play a role in changing the conduction of neurons, because it’s also known, for example, that when MS patients get in a hot tub or take a hot shower, their nerves don’t conduct quite as well and the preexisting symptoms transiently worsen. And this is the kind of story you hear with the premenstrual period. Again, this is distinct from concerns about having a relapse or new symptoms in a new place. So I do think more study is needed to address these changes in preexisting symptoms with the menstrual cycle. But I think it remains to be determined that whether those fluctuations and hormones can be responsible for really modifying the disease course.
Question: Are there any alternative medicines that help with fatigue?
Dr. Bowling: Fatigue is something we often have a difficult time trying to control. As I mentioned in the earlier part of the program, exercise is actually an excellent way to help with fatigue, and that’s something that’s often the last thing you think about doing if you are feeling fatigued. Exercise can be done through conventional means or the unconventional therapies that I’ve talked about. For people who have heat sensitivity, there are various ways to produce cooling and there’s some evidence that cooling strategies can alleviate MS-related fatigue somewhat. A lot of my patients ask me about caffeine—just a simple old cup of coffee or caffeine tablets—and it’s amazing that there aren’t any recent clinical trials in that area. But that’s something that some people report to be helpful.
Question: Why won’t most people avoid a genetic clinical study that might subject them to prejudice of private insurance companies?
Dr. Hauser: This is a very important question. The concerns we all have about the privacy of our genetic information must be taken very seriously by scientists, by universities, and by society. And I assure you that it is. One good example of the way this information is protected for families who are at risk for MS, is the repository of genetic information that’s funded by the National MS Society.
For this repository, patients and their families agree to permit the investigators to obtain a small sample of blood for DNA preparation and then send that DNA to investigators around the world. Their clinical information is included with the genetic sample; however, all of that material and information is immediately uncoupled from all identifying characteristics. So nobody will ever know where that material came from. Name, social security number, address, date of receipt—everything is uncoupled from the material itself. So in this fashion, I think scientists nationwide try to protect people’s confidentiality.
Question: Has B-12 therapy proven effective for MS?
Dr. Bowling: A lot of alternative medicine books actually recommend Vitamin B-12 therapy for MS because it plays an important role in the normal functioning of the nervous system and the immune system. For people with MS, there is a subgroup of people who appear to be vulnerable to Vitamin B-12 deficiency.
As a result, if you’ve been diagnosed with MS, I think it’s very important to have a Vitamin B-12 blood test done at some point in the course of the disease. If the B-12 level is below normal, then Vitamin B-12 therapy is extremely important, and is usually requires lifelong treatment. For people with MS who have normal Vitamin B-12 levels, there’s no good evidence that extra Vitamin B-12 provides an additional benefit. There aren’t any large clinical studies. There was one study done in a limited number of people, in which they treated people with very high doses of Vitamin B-12, tracked them over a 6-to-12 month time period, and found no significant benefit in terms of the disease or various symptoms.
Question: Is therapeutic massage a good idea?
Dr. Bowling: I think that therapeutic massage can provide relief for muscle spasticity. It’s something that can also be helpful for pain. While no formal clinical studies have been done in relation to MS, I certainly have quite a few patients who do it and it’s generally a safe procedure. So for muscle stiffness, relaxation, and pain, I would think about that.
Moderator: In the final few seconds, closing thoughts. Are we optimistic about where we are right now?
Dr. Voskuhl: Well I think that MS research has really grown exponentially over the last decade or two. We know a lot more about the disease and we’ve actually now gotten proven therapies.
I think organizations like the NIH and the National MS Society, and their funding of this research have just grown tremendously, and I think the future is bright. If we continue at the same rate we’ve been going, I think in the near future it looks very bright. Dr. Hauser: I agree. We’ve never been more optimistic. We’ve learned more about this disease in the last decade than we learned in the prior century.
Moderator: That’s all the time we have for today’s North American Education Conference, Reaching for New Frontiers in MS Research. We want to offer our sincere thanks to our presenters. Thanks for being with us.
GENERAL DUGAN: I hope that you leave this program, as I do, encouraged
in knowing that we have brilliant scientists as partners in our fight against
MS, and that we are making progress in understanding this complex disease.
Everything we learn about Multiple Sclerosis leads us closer to defeating
it. At the National MS Society, we want to ensure that the best scientists
in the world are working with us to gain understanding of this disease.
Each of us has a role in making that happen. Whether you work for our cause
as a volunteer or as staff person, make a donation to support our research
mission or recruit a friend to join one of our events, participate in a
clinical trial or take a few minutes to write to your congressman to support
funding for MS research at the National Institutes of Health. Every one
of us has the power to do something to bring us closer to finding the cause
and cure for multiple sclerosis. I am hopeful, and I am optimistic. When
we work together, we will be stronger than this disease. Thank you, and
© 2002 The National Multiple Sclerosis Society