Homecoming

This weekend was my 10 year high school reunion.  Got to see a lot of great people and learn what everyone is up to these days.  It was great to see everyone, but I am a little sad that I didn't get to catch up with everyone; there just was not enough time.  It was a lot of fun though and hopefully we can all get together again soon!  And maybe I will do a better job keeping in touch with people.

And now for the MS info :-)  The following comes from my MSF e-mailer:

Number of Genes Linked to MS More than Doubles
The largest-ever gene study of MS has identified 29 new genetic variants associated with the disease, confirmed 23 previously known genetic links, and suggested five more genes that may contribute to the disease.

Scientists regard the findings, recently published in the journal Nature, as significant for two reasons:  Because many of the genes linked to MS are involved in regulating the immune system –  specifically, the development of T cells – this boosts speculation that the disease is primarily an autoimmune disorder. It also gives researchers new targets for future treatment strategies.

For the study, scientists compared DNA from nearly 10,000 people with MS with DNA from more than 17,000 unrelated, healthy individuals. The researchers were affiliated with the International Multiple Sclerosis Genetics Consortium and the Welcome Trust Case Control Consortium.
They said the newly-found links point to the idea that T-cells – a type of white blood cell responsible for mounting an immune response –   and chemicals called interleukins play a key role in the development of the disease.

Drugs that target the immune system include rituximab, sold under the brand name Rituxan® by Roche and Biogen to fight leukemia, Tysabri® from Biogen and Elan, Lemtrada, sold as Campath® by Sanofi's unit Genzyme for cancer, and Abbott and Biogen's Zenapax® or daclizumab. Mid-stage trial data for daclizumab recently showed the drug on a par with other new medicines for MS, but some of the side-effects were worrisome.

Experts think both genetic and environmental factors are equally important in determining who is likely to develop MS, and taken together, the known genetic variants probably explain about 20 percent of the genetic links, they said.
In a second study reported in the Public Library of Science journal PLoS Genetics, researchers found that many of the genes linked to MS are also linked to other autoimmune diseases such as Crohn's disease and Type 1 diabetes. This also points to potential new uses for existing drugs in development, they said.
Previous research has suggested a link between Vitamin D deficiency and an increased risk of MS. Compston's team said that along with the many genes which play a role in the immune system, they had also found two involved in the metabolism of Vitamin D – which mostly comes from sunlight – lending weight to a possible link between genes and the environment.

"We have known for some time that many devastating diseases of the immune system must have common genetic causes," said Chris Cotsapas of Yale University in the United States, who led the PLoS study. "Now we have the outline of a map that tells us where we can look for common treatments."

In 2007, only three genes were linked to MS.

Research Identifies How Vitamin D Combats MS
New research has indicated that vitamin D directly terminates the production of a disease-causing protein, a discovery that may explain the association between levels of vitamin D in a person’s body and the person’s ability to resist or minimize the effects of MS.

According to the investigators, a collaborative team of scientists from the University of Medicine and Dentistry of New Jersey and Stanford University, the mechanism they identify suggests what might be a new path toward pharmaceutical treatment of MS, as well as therapies for other autoimmune diseases. The mechanism identified by the research team works like this:

During MS (“EAE” in mice), a damaging protein called interleukin-17 (IL-17) is produced by immune cells in the brain.

After vitamin D binds to its receptor, the receptor parks itself on the gene that encodes IL-17.

By doing so, the vitamin D receptor occupies a site normally reserved for a protein called NFAT, which is required to turn the IL-17 gene on.

The gene stays off and IL-17 levels plummet.

At the same time, the vitamin D receptor turns on another gene, whose product generates suppressive T cells that combat the destructive action of their IL-17-producing counterparts.

The study is published in the September issue of the journal Molecular and Cellular Biology.

Unique Trial uses Adult Stem Cells to Treat MS
The Cleveland Clinic, the University Hospitals Seidman Cancer Center, and Case Western Reserve University are collaborating on a one-of-a-kind clinical trial in the United States which uses a person’s own adult stem cells to treat MS and perhaps even reverse damage caused by the disease.

Mesenchymal stem cells, or MSCs, are found in the bone marrow and are not the embryonic stem cells that have stirred controversy in political and religious arenas.

In the phase one trial, a person’s MSCs are harvested, carefully cultivated in a special laboratory and then injected intravenously back into the individual. Since June, three people have undergone the entire process. A total of 24 participants with relapsing or progressively worse MS who have moderate to severe disability will take part in the study over the next two to three years.

The primary aim is to test the feasibility and safety of using the body's own stem cells to treat MS. But researchers also are looking closely for any preliminary evidence that the transplanted cells could moderate the over-active immune system, possibly stopping or even repairing tissue damage.

If promising results lead to a larger, multicenter clinical trial that also yields good outcomes then the treatment could be offered in a clinical setting within five to seven years, researchers involved in the study told the Cleveland Plains Dealer.

More than 150 other clinical trials in the United States and around the world are currently testing MSCs' ability to encourage tissue repair as a way to treat a variety of other conditions such as osteoarthritis, diabetes, emphysema, and stroke. Stem cell therapy is already used to treat leukemia, lymphoma, and certain blood disorders.

 The next post will have more from the MSF e-mailer - there is some really interesting stuff in this most recent e-mailer!  I love learning more about vitamin D and stem cell research!  It is so great that this research continues; I am so hopeful that a cure will come in my lifetime!

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.

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!

Estriol Study

From the NMSS website:

Summary: The National MS Society is funding a team of investigators at 15 medical centers to conduct a two-year, controlled clinical trial of an estrogen (estriol) added to standard therapy to treat MS. Investigators administer either oral estriol along with Copaxone^® (glatiramer acetate, Teva Pharmaceutical Industries Ltd.) or Copaxone plus inactive placebo to 175 women with relapsing-remitting MS. If successful, this clinical trial could lay the groundwork for a larger, definitive trial that could lead to a new treatment option for women with MS, an option that would be a pill, not an injection. Importantly, the exclusion criteria for the study have recently changed, such that patients previously treated with an interferon or Copaxone will no longer be excluded. 
Fifteen Centers Recruiting Patients: The estriol trial is taking place at 15 medical centers across the U.S. Women between 18-50 who are diagnosed with relapsing remitting MS and are interested in participating in this clinical trial should contact the nearest site to discuss their eligibility:

Institution	Coordinator	Phone
UCLA; Dr. Barbara Giesser	Mike Montag	310-794-4020
Washington University, St. Louis; Dr. Anne Cross	Debbie Kemp	314-362-3839
UMDNJ, New Brunswick; Dr. Suhayl Dhib-Jalbut	Yaritza Rosario	732-235-7099
OSU, Columbus; Dr. Michael Racke	Andrea Schertzer	614-366-3757
University of Chicago; Dr. Anthony Reder	Mildred Valentine	773-702-9812
University of Utah, Salt Lake; Dr. John Rose	Julia Klein	801-582-1565 x2014
U. of Texas Southwestern, Dallas; Dr. A. Courtney	Gina Remington	214-645-0560
Johns Hopkins U., Baltimore; Dr. John Ratchford	E'tona Ford	410-502-2489
University of Colorado, Aurora; Dr. John Corboy	Haley Steinert	303-724-4172
U. of New Mexico, Albuquerque; Dr. Corey Ford	Lori Bachert	505-272-8905
U. of Pennsylvania, Philadelphia; Dr. Dina Jacobs	Vanessa Zimmerman	215-349-5162
Dartmouth Med. Sch., Lebanon, NH; Dr. E. Lallana	Laurie Rizzo	603-653-9947
U. of Kansas, Kansas City; Dr. Sharon Lynch	Kelly Dickerson	913-588-0080
U. of Minnesota, Minneapolis; Dr. Gareth Parry	Susan Rolandelli	612-624-5978
Mayo Clinic Arizona, Scottsdale; Dr. D. Wingerchuk	Irene Galasky	480-301-6104

This study, costing more than $5 million, is being funded by the National MS Society – through the support of the Southern California Chapter and other chapters and private donors – and the National Institute of Neurological Disorders and Stroke. Adeona Pharmaceuticals is providing drug for the trial.
Rationale: Estriol levels rise to very high levels naturally during late pregnancy, a time when most women’s MS disease activity declines. This led some to suspect that estriol may be responsible for this easing of symptoms during pregnancy. Dr. Rhonda Voskuhl (University of California, Los Angeles) and others explored this lead in mice with MS-like disease, and later, with National MS Society support, Dr. Voskuhl conducted a small, early-phase trial of estriol in 12 women with MS. Results in mice showed that estriol treatment was indeed protective. Results in the pilot trial showed that estriol treatment decreased disease activity in women with relapsing-remitting MS.
According to Dr. Voskuhl, the trial principle investigator, in using estriol they “aim to simulate some of the disease protection offered by pregnancy. We are very enthusiastic about this new agent since it has decades of known safety and since it will be given as a pill, not a shot.” She further states, "Estriol treatment also has the potential to be more potent in halting disability in MS, since estrogens have been shown in animal models to be not only anti-inflammatory, but also to directly reduce brain injury."
Trial Details/Eligibility: The two-year study is a double-blind, placebo-controlled trial that will take place at 15 sites in the U.S. (listed above). Investigators will administer estriol in pill form to women between the ages of 18-50 who have a diagnosis of relapsing-remitting MS. The oral treatment will be given in combination with subcutaneously injected Copaxone, a standard treatment for MS, for 2 years. The team is evaluating effects of the treatment combination on relapse rates and several clinical and magnetic resonance imaging measures of disability progression.
Contact: For more information, contact the study sites listed above, or please see the study’s listing (NCT00451204) on ClinicalTrials.gov.

If you live in/near one of the above places and are interested in volunteering, be sure to contact the appropriate person ASAP!  This was placed on the NMSS website on 6/10/11 and it didn't say what the deadline is.  I think this is very exciting; I think Estriol has promise based on the previous research I have done regarding Estriol and MS (see Future Therapies Continued (BG-12 & Estriol)).