Happy New Year!

Happy New Year Everyone!  I hope 2012 brings great things!  Hopefully, 2012 will bring the MS community more exciting research, new therapies for ALL types of MS, and leaps closer to a cure.  

In the new year, I resolve to be more active.  My husband and I signed up for a membership with the YMCA.  We had a membership before, but during the time when I was experiencing my first symptoms but before my diagnosis, it became difficult to workout because of the numbness and tingling.  We ended that membership during the fall of 2010, around the time I was diagnosed.  Since then, our "workouts" have mostly consisted of walks around the neighborhood.  Since I have been feeling well for the past year (with a few minor flare-ups in the interim), we decided it was time to get back on the proverbial horse.  I bought a "fitness" swimsuit and plan to do pool workouts to try to avoid heat-induced flare-ups.  Since we signed up a week ago, we have already gone to the Y three times.  I have not started the pool work yet, but plan to this week.  Our NMSS local chapter has a wellness theme this year and in keeping with that, my goal is to get/stay fit and healthy. 

What is your resolution?

In news, researchers have confirmed a link between MS and a gene linked to vitamin D deficiency.  To read more, click here.  I knew that I was smart to be taking vitamin D supplements.  I had my levels checked and was low - I definitely believe that there is a critical link between vitamin D and MS - this research seems to confirm that!

New MSF Mailer - Part II

Happy Labor Day!  I hope everyone has enjoyed the long weekend!  Now, for more from the MSF mailer:

New Research on Breastfeeding with MS Contradicts Previous Findings

Despite previous research suggesting otherwise, breastfeeding does not appear to protect against MS relapses, according to researchers from the University of Florence in Italy. Their study found that the likelihood of relapse after pregnancy was tied to relapses before and during pregnancy but not to whether the mothers in their study breastfed or not. They concluded breastfeeding may not be a feasible option for mothers at high risk of relapse after pregnancy, because they may need to resume drug treatments straight away.
Study author Dr. Emilio Portaccio and colleagues conducted a prospective study of 298 women recruited from 21 Italian MS centers and followed up their pregnancies from 2002 to 2008. During this time, 302 out of 423 pregnancies resulted in full-term delivery, and follow ups continued for at least one year after delivery. About 34 percent of the mothers breastfed for at least two months after delivery, while the remaining mothers breastfed for less than this or not at all and were considered as not breastfeeding. During the 12 months following delivery, 37 percent of the mothers had one relapse and 6.6 percent had two or more.
Using a statistical tool to look at several measures at once to see which have the strongest influence on relapse rate after pregnancy, they found that "the only significant predictors of postpartum relapses were relapses in the year before pregnancy ... and during pregnancy."
The data indicated women who had relapses in the 12 months leading up to their pregnancy were 50 percent more likely to have a relapse after delivery than women who did not have a relapse in the year before pregnancy. And women who had relapses during pregnancy were more than twice as likely to have a relapse after delivery as the women who did not experience relapses during pregnancy.
This was after taking into account influencing factors like age at onset of MS, age at pregnancy, duration of the disease, level of disability, and exposure to drugs, including any MS drugs. There was nothing to suggest breastfeeding worsened the relapse rate.
The researchers also suggested the link between breastfeeding and lower risk of relapses after pregnancy that previous studies have reported may "simply reflect different patient behavior, biased by the disease activity."

"Women who have fewer relapses before and during pregnancy may be more likely to breastfeed and then continue to have fewer relapses in the postpartum period," Portaccio says. However, he said that a course of steroids taken after pregnancy might protect against later attacks, and adds, "Approaches of this type were not assessed in this study and might, in consultation with the treating neurologist, enable breastfeeding."  The study was published in the journal Neurology.

Author Brings Cool Thoughts on Cognition when Heat Meets MS

The fact that heat can cause MS physical symptoms to flare has been well-established, but recent research has shed more light on the problems, confirming what people with MS already know:  Heat can further complicate the cognitive difficulties caused by the disease. Jeffrey Gingold, an award-winning author with MS and volunteer advocate on MS and cognitive disability, recently described his reactions to the research and to the “cognitive sludge” created by rising temperatures. You can read his article, “Cool Thoughts” in the Men and MS column in the summer issue of the MSFocus.
The second edition of Gingold’s popular book Facing the Cognitive Challenges of Multiple Sclerosis (Demos Health, 2011) was recently released. In it, he candidly describes his personal journey from MS diagnosis to learning how to cope with the many challenges the disease brings.  In Mental Sharpening Stones: Manage the Cognitive Challenges of Multiple Sclerosis (Demos Health, 2008) Gingold provides more real-life techniques that have been used with success by people with MS and their medical providers to pushing back against the disruptive and potentially disabling cognitive symptoms.
For a limited time, a 30 percent discount is being offered for those who buy the books at www.demoshealth.com.  Just enter the discount code SSGINGOLD30 during checkout and the percentage will automatically be deducted before checking out. There is an expiration date of 5/31/2013 for the discount.  
One hundred percent of the author’s royalties from the two books are donated to MS research and education.

A Study of Ocrelizumab in People with Primary Progressive MS

This randomized, parallel group, double-blind, placebo controlled study will evaluate the efficacy and safety of ocrelizumab in people with primary-progressive MS. Eligible patients will be randomized 2 to 1 to receive either ocrelizumab (300 mg intravenously, 2 infusions separated by 14 days in each treatment cycle) or placebo. The blinded treatment period will be at least 120 weeks, followed by open label treatment for people in both groups who, in the opinion of the investigator, could benefit from further or newly initiated ocrelizumab treatment. Anticipated time on study treatment is up to five and a half years.
For information on study locations and inclusion criteria go to www.clinicaltrials.gov and search for identifier number NCT01194570.

 I am amazed at the immense impact MS has on the body and mind.  MS truly affects every aspect of life, maybe not all day every day, but it sticks its nasty head in whenever it feels like it and in whatever way it wants.  It can affect balance, coordination, ability to walk, feeling, sleep, thought processes, memory, etc, etc, etc.  The list goes on and on and on.  Don't you just wish that there was something that it couldn't touch?  Hopefully all this great research will lead to a cure!  Continuing to be optimistic although some days that isn't easy.

New MSF Mailer - Part I

More news to be excited about!  This post (and the next post) contains information set forth in my latest MSF mailer.

First, interesting stuff about Myelin:

Myelin Influences How Brain Cells Send Signals

Myelin is well-known for its protective role in the central nervous system, but recent research suggests that myelin also plays a role in regulating a key protein involved in sending long-distance signals. The development of a new cell-culture system that mimics how specific nerve cell fibers in the brain become coated with protective myelin led to the discovery.

Ohio State University researchers have created a system in which two types of cells interact in a dish as they do in nature: neurons from the hippocampus and other brain cells, called oligodendrocytes, whose role is to wrap myelin around the axons.

MS has long been considered a disease of white matter, a reference to the white-colored bundles of myelin-coated axons that project from the main body of a brain cell. But researchers have discovered that the condition also affects myelinated axons scattered in gray matter that contains main bodies of brain cells, and specifically the hippocampus region, which is important for learning and memory.

Up to half of the people who have MS experience cognitive deficits in addition to physical symptoms. Researchers suspect that cognitive problems are caused by abnormal electrical activities of the demyelinated axons extending from hippocampal cells, but until now have not been able to test myelin's role in this part of the brain.

Now that the researchers can study how myelination is switched on and off for hippocampal neurons, they also can see how myelin does more than provide insulation – it also has a role in controlling nerve impulses traveling between distant parts of the nervous system. Identifying this mechanism when myelin is present will help improve understanding of what happens when axons in this critical area of the brain lose myelin as a result of MS, researchers say.

 Second, bone health is important and more about vitamin D:

Bone Health a Factor in Early MS

Osteoporosis and low bone density are common in people in the early stages of MS, according to a new study.
“We’ve known that people who have had MS for a long time are at a greater risk of low bone density and broken bones, but we didn’t know whether this was happening soon after the onset of MS and if it was caused by factors such as their lack of exercise due to lack of mobility, or their medications or reduced vitamin D from lack of sun exposure,” said study author Stine Marit Moen, M.D., of Oslo University Hospital Ulleval in Norway.
Low vitamin D levels are associated with an increased risk of MS. Low vitamin D levels can lead to reduced calcium absorption and bone mineralization, or the process the body uses to turn minerals into bone structure.
“Our hypothesis was that if vitamin D exerts a major effect on the risk of MS, then the effects of low vitamin D levels on bone density would be apparent soon after the onset of MS,” Moen said.
The study involved 99 people with an average age of 37 who were recently diagnosed with MS or clinically isolated syndrome, which means they had a first episode of symptoms like those in MS but have not yet been diagnosed with the disease. All had no or minor physical disability from the disease.
The participants had bone density tests an average of 1.6 years after the first time they had any symptoms suggestive of MS. Their tests were compared to bone tests of 159 people of similar age, gender, and ethnicity who did not have the disease.
A total of 51 percent of those with MS had either osteoporosis or osteopenia, compared to 37 percent of those who did not have the disease. Osteoporosis is a disease where low bone density causes the bones to become thin and brittle, making them more likely to break. Osteopenia is low bone density that is less severe than osteoporosis but puts a person at risk for osteoporosis.
The results remained the same after researchers adjusted for other factors that can affect bone density, such as smoking, alcohol use, and hormone treatment.
“These results suggest that people in the early stages of MS and their doctors need to consider steps to prevent osteoporosis and maintain good bone health,” Moen said. “This could include changing their diet to ensure adequate vitamin D and calcium levels, starting or increasing weight-bearing activities and taking medications.”

The study was published in Neurology, the medical journal of the American Academy of Neurology.

Third, more on understanding MS:
 

MS-Like Disease in Monkeys may Yield Helpful Clues 

The discovery of a naturally occurring disease in monkeys that is very much like MS in humans could have a major impact on efforts to understand the cause of the disease. The disease that researchers from Oregon Health & Science University (OHSU) discovered in monkeys at the Oregon National Primate Research Center is associated with a herpes virus that could give significant clues into how MS develops in humans. MS researchers have long believed that a type of herpes virus may trigger multiple sclerosis in people who are genetically susceptible to the disease.  

"These findings could have a huge impact on our understanding of MS and could be a landmark in someday developing more effective treatments for the disease, or even methods to prevent the onset of MS," said Scott Wong, Ph.D., senior author of the study and a scientist at the Vaccine and Gene Therapy Institute and the Oregon National Primate Research Center.
Before the OHSU findings, researchers had been able to study MS-like diseases in nonhuman primates only after the disease had been artificially induced. A naturally occurring disease, such as the one discovered at OHSU, can give researchers many more clues into the causes and development of the disease.
"Now, we may be able to tease apart what's triggering the onset of the disease," Wong said.
And the fact that the disease, found in a small percentage of the Japanese macaques at OHSU each year, came from a herpes virus could prove hugely important to MS researchers worldwide. Researchers can now search for a similar virus in people with MS.
From 1986 through 2010, 56 of the Japanese macaque monkeys at the Oregon National Primate Research Center at OHSU spontaneously developed paralysis in their hind limbs, along with other symptoms. The monkeys were humanely euthanized because they could not have been returned to the monkey colony safely. Researchers later did necropsies on their bodies and performed MRI scans on eight of the animals.
That work and other testing allowed researchers to discover that an MS-like disease called Japanese macaque encephalomyelitis was causing the paralysis. While the disease typically afflicted young adult animals, it also was present in juveniles and older animals, and was present in both males and females.
About 1 to 3 percent of the more than 300 Japanese macaques at the primate center develop the disease each year, according to the researchers.
With this discovery, MS researchers now will be able to move toward trying to prevent or treat the virus in monkeys, which might help scientists make progress in treating MS in humans. The OHSU researchers' findings were published online in the Annals of Neurology.

Always nice to know that they have found a possible cause of MS - maybe a virus is to blame!

Phase III Trial Results (Alemtuzumab & Laquinimod)

From the NMSS's website, the results of Phase III trials:

First, Alemtuzumab:

Sanofi and its subsidiary Genzyme have announced that the experimental intravenous therapy alemtuzumab (with a proposed brand name Lemtrada,™) met one of two primary endpoints by significantly reducing relapse rates in a two-year study comparing two annual cycles of alemtuzumab against standard subcutaneous dosing of Rebif^® (interferon beta-1a, EMD Serono Inc. and Pfizer). The study, called CARE-MS I, involved 581 people with early relapsing-remitting MS. The study did not meet its second primary endpoint of slowing disease progression compared to Rebif. The results were announced in July 11 press release. Data analysis is ongoing and the company expects to provide a full report at an upcoming medical meeting. Another trial of alemtuzumab, called CARE-MS-II, is currently underway.
Background: Multiple sclerosis involves immune system attacks against brain and spinal cord tissues. Alemtuzumab is a humanized monoclonal antibody directed at CD52 (a protein on the surface of immune cells) that is currently approved by the U.S. FDA for the treatment of B-cell chronic lymphocytic leukemia. Its ability to target immune cells led investigators to test its potential as a treatment for relapsing-remitting MS. An earlier phase II study compared two dose levels of alemtuzumab with Rebif in 334 subjects with relapsing-remitting MS who had never taken any other disease-modifying therapies. Those taking alemtuzumab had a 74% reduction in the risk of MS relapse compared with those on Rebif, and a 71% reduction in the risk for sustained accumulation of disability (New England Journal of Medicine 2008 359;17: 30-45).
Dosing was temporarily suspended in the Phase II study due to the occurrence of immune thrombocytopenic purpura (ITP), a rare condition in which low blood platelet counts can lead to abnormal bleeding. After the first cases of ITP occurred, one of which was fatal, Genzyme implemented a patient safety monitoring program which includes patient and physician education and regular contacts with patients. Two phase III studies comparing alemtuzumab with Rebif were then launched.
In June 2010, it was announced that alemtuzumab had been designated by the FDA as a “Fast Track Product.” This designation should expedite its future review by the FDA after the company submits results of the phase III trials. The press release stated that the company expects to file for regulatory approval of alemtuzumab for MS in early 2012.
This Study: In the CARE-MS I study, approximately 581 people with early, active relapsing-remitting MS, who had never received disease-modifying therapy to treat their MS, were randomly assigned to receive alemtuzumab or Rebif. Alemtuzumab was given by intravenous infusion for 5 days initially and for 3 days one year later. Those on Rebif received the standard dose of 3-times weekly subcutaneous injections. According to the press release, after two years the relapse rate of those on alemtuzumab was reduced by 55 percent compared to those on Rebif. After two years, 8 percent of those on alemtuzumab had an increase in their EDSS score (a standard scale of physical disability) compared to 11 percent on Rebif – a difference that was not statistically significant.
According to the press release, the most common adverse event associated with alemtuzumab in the CARE-MS I study included reactions associated with infusions (such as headache, rash, fever, flushing, hives and chills). There were more infections in those taking alemtuzumab, predominantly mild to moderate, and there were no fatal infections. Less than 20 percent on alemtuzumab developed autoimmune thyroid-related problems and less than one percent developed ITP.
In the ongoing CARE-MS II study, approximately 1200 subjects at over 250 study sites have been randomly assigned to receive one of two alemtuzumab treatment regimens, or Rebif.
Comment: These positive results are the first reported from this Phase III study of alemtuzumab. Full details and evaluation of this study, and from another Phase III study now underway, should help define the safety and promise of alemtuzumab as a potential new therapy for relapsing MS.

Next,  Laquinimod:

Teva Pharmaceutical Industries Ltd. and Active Biotech announced in a press release that the phase III BRAVO study, in which the experimental oral drug laquinimod was tested against inactive placebo in a study involving over 1300 people with relapsing-remitting MS, did not reach its primary goal of reducing the average number of relapses in a year. However, when the investigators adjusted the data to correct for differences in magnetic resonance imaging characteristics at the start of the study, a significant reduction in average annual relapse rate was observed in the group receiving the laquinimod. Further analysis is ongoing, and the results are being submitted for presentation at a scientific meeting later this year. The companies state that they plan to submit applications to regulatory authorities for the treatment of MS in the United States and European Union.
Background: Multiple sclerosis occurs when the immune system mistakenly attacks nerve fiber-insulating myelin and other brain and spinal cord tissues. Laquinimod is a monoclonal antibody believed to affect the immune attack. In an earlier phase II study involving 306 people with relapsing-remitting MS, oral laquinimod reduced disease activity by 40.4% compared with inactive placebo. (Lancet 2008; 371: 2085–92) In one phase III study – the ALLEGRO study – laquinimod reduced the annual relapse rate in those completing the trial by 23%, compared to those on placebo. (Late-Breaking News – American Academy of Neurology, 2011)
The Study: In the BRAVO study, participants were randomly assigned to receive either laquinimod 0.6 mg (one capsule daily), inactive placebo, or Avonex® (interferon beta-1a, Biogen Idec) 30 mcg/wk for 24 months. The primary goal of the study was to determine the effect of laquinimod on the rate of relapses. Secondary goals included impacts on disease activity as observed on MRI scans, and accumulation of disability. Laquinimod was not directly compared to Avonex, but just to the inactive placebo.
Laquinimod did not reduce the annualized relapse rate significantly more than placebo. According to the press release, there were differences in MRI characteristics between the treatment groups at the beginning of the study, and when the data were adjusted to account for these differences, laquinimod was found to reduce annualized relapse rate, disability progression (as measured by the EDSS scale of disease activity), and brain tissue volume loss significantly more than placebo. No details were released related to safety, except to state that “laquinimod demonstrated a favorable safety and tolerability profile compared to placebo.”
According to the companies, further analysis is ongoing, and the results are being submitted for presentation at a scientific meeting later in the year. The companies plan to submit applications to regulatory authorities for the treatment of MS in the United States and European Union. The complete data from the BRAVO and ALLEGRO studies should help define the safety and promise of laquinimod as a potential new oral therapy for relapsing-remitting MS.

Always nice to know what progress is being made!

New from the NMSS website

The following was found on the NMSS website about topics discussed at the recent Consortium of MS Centers annual meeting:

The core purpose of the Consortium of MS Centers (CMSC) is to maximize the ability of MS healthcare professionals to impact care of people who are affected by MS, thus improving their quality of life. The CMSC recently held its 25th annual meeting in Montreal, featuring more than 200 reports on research to improve care and quality of life of people with MS. Download the entire book of scientific abstracts from the CMSC meeting (PDF). Here is a small sample of these reports:
Exercise boosts cognitive function: Cognitive changes are common in people with MS -- as many as half of people with MS will develop problems with cognition. Brian Sandroff and colleagues (University of Illinois, Urbana) enrolled 42 people with MS who wore accelerometers for seven days, and were administered tests of cognitive function. More physical activity was associated with faster information processing speeds, independent of a person’s disability status. In a similar effort, the National MS Society is currently funding a trial comparing the ability of aerobic exercise versus a stretching program to improve cognitive performance. (Abstract #S22)
Fatigue: MS predictor? Fatigue is one of the most common symptoms of MS, and may be the most prominent symptom in a person who otherwise has minimal activity limitations. Joseph Berger, MD, and colleagues (University of Kentucky, Lexington) looked at the frequency with which fatigue “heralds” the onset of MS. Among 5305 people with MS, 29% reported fatigue in the three years before MS diagnosis. In 30% of these patients, fatigue was the only symptom preceding MS diagnosis. Fatigue preceded MS diagnosis by an average of 501 days. The authors advise that, in people experiencing unexplained fatigue, a detailed neurologic history and exam should be conducted to rule out MS. (Abstract #P18)
Wii™ for improving balance: Balance can be difficult to maintain for people with MS. Erin Korsbrek, MSc, and colleagues (University of Calgary) enrolled 18 people with MS in a study using Nintendo Wii Fit Plus three times per week for six weeks. Functional balance improved, and measures of fatigue and other symptoms remained stable, indicating no adverse effects. Coauthor Maureen Dunn, PhD (Hope College, Holland, MI) is currently funded by the National MS Society to conduct a 12-week trial to determine whether Wii is an effective balance rehabilitation tool for people with MS. (Abstract #P21)
Resveratrol: Negative preclinical results: The CMSC meeting includes laboratory studies as well. Previous research has suggested that resveratrol, a component of red wine, enhances the activity of a molecule (SIRT1) that might help to preserve nerve fibers, and it has been shown in several studies to decrease the severity of the MS-like disease EAE in mice. Fumitaka Soto, PhD (Louisiana State University, Shreveport) and colleagues reported that resveratrol actually worsened EAE in mice, causing severe damage. Further research will be needed to sort out this question. (Abstract #S7)
Evaluating relationship education: “Relationship Matters: A Program for Couples Living with MS” was developed by the National MS Society to help couples affected by MS to strengthen their partnerships and minimize the impact of MS on their lives. Couples receive eight hours of programming via “teleclasses” or in-person workshops. Kimberly Koch, MPA (National MS Society) and colleagues looked at a sample of more than 1,000 participants, and found significant increases in relationship satisfaction, along with clinically significant improvement in mental health. Funding for this project was provided by the United States Department of Health and Human Services, Administration for Children and Families, Grant: 90FE0090.
Read more about this program. (Abstract #S8)
Risk tolerance for MS therapies: Recently, several more effective, but more risky, therapies have become available to treat MS, and more are under development. Society grantee Robert Fox, MD (Cleveland Clinic Foundation) and colleagues administered a web-based questionnaire on risk tolerance to more than 10,000 people enrolled in the North American Research Committee on MS (NARCOMS) registry. A total of 5,446 people completed the questionnaire, and the results showed that three factors were associated with increased tolerance for risky therapies: increased disability, male gender, and not currently being on an MS treatment. These results can help to guide discussions between clinicians and people with MS. (Abstract S84)
Psychosocial factors related to smoking: Research suggests that smoking may increase the risk of developing MS and may speed disease progression. Joseph Ostroff and colleagues (State University of New York, Buffalo) examined factors that distinguished smokers from nonsmokers in a sample of 1300 people with MS whose information was recorded in the New York State MS Consortium registry. Smokers were significantly more likely to be single or divorced, and to experience higher levels of pain, fatigue, tension, and loneliness. Read more about healthy living with MS. (Abstract #S91)
Air travel accessibility: The challenges of traveling with a disability were discussed in focus groups and in visits to the local airport by a team including the St. Louis VA MS Center and Spinal Cord Injury Service, the Gateway Chapter of the National MS Society, Paralyzed Veterans of America, the St. Louis Americans with Disabilities Act (ADA) coordinator, and local airport, airline, and Travel Security Administration staff. Targets for accessibility improvement were identified, including the need to train airport staff regarding wheelchair mechanics and batteries; the need to provide opportunities for travelers with disabilities to do “dry runs” to increase familiarity; and the need to improve signage to indicate accessible routes to baggage claim. Read more about travel tips for people with MS. (Abstract #S124)
Educating physical therapy students about MS: Angela Rosenberg, PT, DrPH (University of North Carolina, Chapel Hill) and colleagues, including Kaye Gooch of the Society’s Eastern North Carolina Chapter, presented a program developed by the university and chapter to educate physical therapists in the management of the neurologic and psychosocial needs of people with MS. Evaluations of the program indicate increases in MS-specific knowledge, and the team hopes this two-year program will serve as a model for other universities. Read more about education opportunities for physical and occupational therapists provided by the National MS Society. (Abstract #S133)
Breathing problems during sleep: Sleep-disordered breathing is a problem of respiration that occurs during sleep, such as sleep apnea. Tiffany Braley, MD, a Sylvia Lawry Physician Fellow of the National MS Society, explored the occurrence of these disorders in 48 people with MS and 84 controls without MS. The results suggest that people with MS and disease activity in the brainstem (the lower extension of the brain where it connects to the spinal cord) had a predisposition for sleep-disordered breathing. People with these disorders reported fatigue, lack of energy, or tiredness to be their most problematic symptom, as opposed to excessive daytime sleepiness. Read more about sleep disorders in MS. (Abstract #S155)
Click here to view the entire book of scientific abstracts from the CMSC meeting (PDF).

Interesting news as always!  Looks like I really need to be better about exercising - need to keep my cognitive functioning up!  My husband and I used to have a Wii, but we sold it when we stopped using it; now I kind of wish I still had it to improve my balance.  Surely, there are other things I can do to help improve balance.

CCSVI Research Progress Report

I received an email today about the NMSS's ongoing research related to CCSVI.  The following article is posted on the NMSS's website:

The first-year progress reports from seven multi-disciplinary teams investigating CCSVI (chronic cerebrospinal venous insufficiency) in MS indicate that they are on track to provide essential data and critical analysis as these two-year projects move toward their completion. These studies were launched on July 1, 2010 with a more than $ 2.4 million commitment from the MS Society of Canada and the National MS Society (USA).
The research teams have already recruited a broad spectrum of people with MS and others to build understanding of who may be affected by CCSVI. In addition they are refining CCSVI imaging methods for accuracy and consistency in order to reliably validate the occurrence of CCSVI and understand its implications in the MS disease process.
Representatives of each of the seven funded teams are part of the Canadian Institutes of Health Research (CIHR)’s Scientific Expert Working Group. Following a meeting of the working group in June 2011, the Canadian Federal Minister of Health, the Honourable Leona Aglukkaq, announced a Phase I/II interventional clinical trial on CCSVI. The working group will provide leadership and advice in the drafting of the terms of reference for the Phase I/II clinical trials in Canada, and will continue to monitor and analyze the data from the seven studies and other studies related to CCSVI and MS around the world.

Regarding the seven funded teams, all have received approval for their studies from the required Institutional Review Boards in the U.S. or the Research Ethics Board in Canada, a first step established by regulatory authorities to protect human subjects involved in research projects. (Read more about steps involved in conducting clinical research.)
Already more than 486 people have undergone scanning with various imaging technologies being used by the studies, including the Doppler ultrasound technology originally used by Dr. Paolo Zamboni and his collaborators, as well as magnetic resonance studies of the veins (MR venography), catheter venography, MRI scans of the brain, and clinical measures.
Because the studies employ rigorous blinding and controls designed to collect objective and comprehensive data, the full results of the ongoing research will be available only after completion of the studies which will involve more than 1300 people representing a spectrum of MS types, severities and durations, as well as individuals with other disease types and healthy controls. In the meantime, several teams are planning to present preliminary results at medical meetings later this year.
“We are pleased that this important work investigating the link between CCSVI and MS is advancing quickly,” notes Dr. Tim Coetzee, chief research officer at the National MS Society. “Results from these comprehensive studies will help inform important next steps.”
Yves Savoie, President and chief executive officer of the MS Society of Canada concurs, “The CIHR’s Scientific Expert Working Group, who will provide leadership and advice in the drafting of the terms of reference for the Phase I/II clinical trials in Canada, will continue to monitor and analyze the data from these studies and other studies related to CCSVI and MS around the world. We are heartened to be moving closer to more definitive answers about CCSVI and MS.”
Details: The funded investigators, who are drawn from a broad range of disciplines ranging from MS neurology, vascular surgery and interventional radiology, report progress in establishing standardized protocols, recruiting and scanning participants and in the development of plans for sharing their findings, as summarized below.
• Dr. Brenda Banwell, The Hospital for Sick Children, Toronto, Ontario:
To determine whether signs of impaired vein drainage might be present early in the MS disease course, Dr. Banwell’s team received approval from the Research Ethics Board and then began enrolling children and teenagers who have MS, and healthy controls of the same age. They are seeking venous abnormalities using non-invasive MRI measures of vein anatomy and novel measures of venous flow, as well as ultrasound. Unlike adults with MS, children are unlikely to have age-related changes in blood vessels, and are less likely to have adult health conditions such as high blood pressure or heart disease, which might otherwise complicate findings. The team’s ultrasound team received training in Dr. Zamboni’s original techniques from the Buffalo Neuroimaging Analysis Center, and they have created ultrasound and brain imaging procedures suited to explore venous drainage in children. Dr. Banwell’s team reports that recruitment is going well, and that they plan to analyze findings only after all 90 participants have undergoing the testing. Read details of Dr. Banwell’s original study plans.
• Dr. Fiona Costello, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta:
Once her team received Research Ethics Board approval, they began recruiting a cross-section of people with MS who would be compared with those affected by other neurological diseases or healthy volunteers. They have three dedicated ultrasound technologists who have been trained to do scanning as originally done by Dr. Zamboni, and they have refined their scanning protocol. The team is planning to repeat scans on a subset of participants who had been scanned before they made method changes, which will allow them to compare the sensitivity of results pre- and post-training. Dr. Costello’s team slowed recruitment briefly to upgrade to a new 3 Tesla (3T) MRI scanner (twice as strong as standard clinical MRI), and they have expanded their MRI team to include two additional, experienced members. The 3T machine went online in March 2011 and it is now being used to perform MR venography scans to compare against the ultrasound tests. Read details of this team’s original study plans.
• Dr. Aaron Field, University of Wisconsin School of Medicine and Public Health, Madison:
His team is now actively recruiting participants to undergo MR venography and ultrasound techniques originally used by Dr. Zamboni to investigate CCSVI in people with early and later stages of MS, controls with other conditions and healthy volunteers, now that they have received approval of the study from the Institutional Review Board. Their ultrasound expert has received training in the Zamboni techniques. The team has refined its MR venography protocol to account for variations in blood flow that occur with breathing and heartbeats. They have determined that they will use a relatively new contrast agent or dye that will permit high-quality images of the veins in the head and neck and for measuring blood flow in the brain. This will enable the entire MRI/MRV exam to be completed with one time-saving injection instead of two. They have also standardized locations along the length of veins where they take blood flow measurements because they have found large differences in both anatomy and size of head and neck veins. The team has submitted a meeting abstract reporting on their protocol development for consideration at the International Magnetic Resonance Angiography Workshop to be held September 25-28, 2011 in Calgary, Alberta, Canada. Read details of this team’s original study plans.
• Dr. Robert Fox, Cleveland Clinic Foundation, Cleveland:
After his team received IRB approval for using MR venography, ultrasound, MRI and clinical measures in people with MS or who are at risk for MS (CIS) and comparison groups, they began recruiting and scanning participants. The ultrasound team, which underwent training in the technique originally used by Dr. Zamboni, found several aspects of the published methodology ambiguous, and they have standardized the protocol and analysis to achieve consistent results.
They shared their solutions to these methodological challenges in a poster presented at the American Academy of Neurology’s annual meeting in April 2011 (Abstract P01.263). The poster outlined physiological and technical factors that can complicate screening for vein blockages using ultrasound, including that heartbeat irregularities, stages of breathing, head position and pressure applied by the operator could alter results; and that the state of hydration of the subject (whether they drank adequate amounts of fluids) could impact results of several of the criteria used to determine CCSVI. They concluded that these complications may help explain the mixed results reported thus far related to CCSVI and MS, and they have added to their aims a study designed to evaluate the impact of hydration on CCSVI assessments.
Dr. Fox’s team has also gathered autopsy specimens of venous tissue from 9 MS tissue donors and 6 donors who did not have MS. The team first had to develop and standardize techniques for studying these specimens for signs of CCSVI. They are analyzing their data and have submitted abstracts reporting preliminary findings related to this pathology study and their scanning results for consideration at the international ECTRIMS (European Committee for Treatment and Research in MS) meeting in October 2011. Read details of this team’s original study plans.
• Dr. Carlos Torres, The Ottawa Hospital, University of Ottawa, Ontario:
His team obtained Research Ethics Board approval after negotiating details over elements of the informed consent form used to explain the study’s procedures and potential outcomes to participants. The team has been conducting the first phase of scanning, using MRI and MR venography, in people without MS, which will be used to compare with various scans in people with MS. Three team members have been trained using the ultrasound techniques originally used by Dr. Zamboni, and they are on track recruiting more participants for the study. Dr. Torres expects to finalize phase 1 of the study by the end of the summer and then will move on to phase 2, which involves people with MS and other controls. Read details of this team’s original study plans.
• Dr. Anthony Traboulsee, UBC Hospital MS Clinic, UBC Faculty of Medicine and Dr. Katherine Knox, Saskatoon MS Clinic, University of Saskatchewan:
After both sites received Research Ethics Board approval they began to recruit, they have scanned a significant number of participants, and the level of interest in the MS community remains high. Their ultrasound technologists were trained by Dr. Zamboni, and they are also using catheter venography and MR venography to investigate the prevalence of CCSVI in people with MS and controls without MS. After the radiologists at both sites met in February 2011 to ensure the consistency of their protocols, they did a second wave of recruitment and hope to finish all testing before the end of 2011. Read details of their original study plans.
• Dr. Jerry Wolinsky, University of Texas Health Science Center at Houston: After receiving IRB approval, the team began recruiting participants, and their neurosonographer received intensive training for intracranial and extracranial ultrasound scanning techniques. The team has already scanned a significant number of participants, which include people with different types of MS, people with other conditions, and people with no known health problems. The team is testing whether other imaging methods can confirm the ultrasound findings, while identifying the most reliable technique to screen for CCSVI. Dr. Wolinsky’s team continues to encounter difficulty in recruiting non-MS control subjects who don’t have a personal interest in the purpose of the trial. The executive committee that oversees this study has agreed with the team’s plan to continue aggressively recruit other controls, while at the same time increasing the number of MS participants. In some cases they have also found that some participants who were contacted to go into the next phase of scanning informed the investigators that they had gotten the venoplasty procedure, which made them ineligible to continue in the study. Read details of this team’s original study plans.
Going Forward: These seven teams were chosen by an international panel of experts that included specialists drawn from all key relevant disciplines including radiology, vascular surgery and neurology. The projects were selected for having the greatest potential to quickly and comprehensively determine the significance of CCSVI in the MS disease process. (Read more)
At this one-year milepost the investigators are making significant progress on their overall two-year study goals. The teams are making plans for sharing preliminary results at upcoming medical meetings, and have demonstrated a clear willingness to share technical advice so that the projects can move forward as smoothly and quickly as possible. Their results will help guide the development of a phase I/II clinical trial recently announced by the Canadian Federal Minister of Health to test whether treating vein blockages may be safe and effective in treating people with MS.
The next update on the work of the seven grantees will be reported in six months.

Very interesting!  Sorry for the lengthy post, but I didn't want to leave anything out on this.

Research Research Research!

I have been pretty tired lately, but I am determined to continue to post at least once per week!

I just got around to reading emails that have been accumulating for the past few days and I learned that recently the National MS Society (NMSS) committed $17.5 million to support 50 new MS research projects.  This is all "part of its comprehensive strategy to stop MS in its tracks, restore function that has been lost, and end the disease forever."  The following is from the NMSS website:

To find the best research projects, the National MS Society relies on more than 70 world-class scientists. These scientists volunteer their time to carefully evaluate hundreds of proposals every year.
The new projects support the comprehensive research goals outlined in the Society’s five-year Strategic Response, including an increased focus on understanding and stopping disease progression, supporting development of new therapies, identifying rehabilitation and other strategies to restore function, and getting more researchers and scientists focusing on MS. The new projects include:

• clinical trials testing whether vitamin D can stop MS activity
• a clinical trial to evaluate whether a repurposed drug, phenytoin, can protect the nervous system from MS damage;
• investigations of mechanisms that may lead the immune system to turn against the nervous system;
• studies of natural molecules that may stimulate repair of the nervous system to restore function; 
• studies exploring novel exercise programs to combat MS symptoms; and
• a study comparing the activity of several viruses, including Epstein-Barr virus, that may be involved in triggering immune attacks in people with MS, which may lead to clues to ending MS through prevention. 

This is so great!  I am so happy to know that so much research is ongoing!  I am also glad to know that all of that money we all raise every year for Walk MS, Bike MS and a number of other NMSS events is going toward all of this exciting research!  I am especially excited to learn more about this Vitamin D theory.  Personally, I have been taking Vitamin D supplements since the Valentine's Day teleconference and I would love to know if those are helping in any way.

I also learned that the oral drug BG-12, which I previously posted about here, which is in clinical trials recently reported some positive results.  The following are excerpts from the NMSS website:

Biogen Idec announced that the experimental oral therapy BG-12 significantly reduced the proportion of people with MS who experienced relapses in a two-year study of more than 1200 people with relapsing-remitting MS. Although its exact mode of action is not known, BG-12 is thought to inhibit immune cells and molecules involved in MS attacks on the brain and spinal cord. The results were announced in an April 11 press release. Data analysis is ongoing and the company expects to provide a full report at an upcoming medical meeting. Another trial of BG-12 is currently underway.
In an earlier phase 2 study, compared to inactive placebo, the highest tested BG-12 dose led to a 69% reduction in active inflammation on MRI scans from weeks 12 to 24. Side effects (formally known as adverse events) included abdominal pain, flushing, headache, fatigue, and feeling hot.
The primary goal of the DEFINE study was to determine whether BG-12 could decrease the proportion of participants experiencing relapses and whether the agent was safe and well tolerated. Secondary objectives included assessing BG-12’s effects on the frequency of relapses, disability progression, and disease activity detected by MRI.
Participants were randomly assigned to one of two treatment groups receiving different doses, or a group receiving placebo. According to the press release, in both groups taking BG-12, the primary endpoint was met, meaning a significant reduction in the proportion of people experiencing relapses at 2 years. All secondary endpoints were met as well in these groups, with significant reductions in relapse rate, disease activity on MRI scans, and in disability progression as detected by the EDSS, a standard scale that measures disability. According to the press release, adverse events were similar to those experienced during the Phase 2 study (those included abdominal pain, flushing, headache, fatigue, and feeling hot):
These positive results are the first reported from this large, Phase 3 study of BG-12. Full details and evaluation of this study, and from another Phase 3 study now underway, should help define the safety and promise of BG-12 as a potential therapy for relapsing MS.

More good news!  Maybe soon a second oral therapy will be available!  That is enough news for one night, but everyone should also check out the Emerging Therapies Collaborative at this website.  Also, if you have a chance, you should check out this MS blog.

Hope everyone reading is well!  Look forward to another post by the end of the weekend!