RMMSC Clinical Research Study on Tysabri: An Interview with Dr. Augusto Miravalle

dr augusto mirravalle

Dr. Miravalle, could you please describe the approach and purpose of the Tysabri study?

The Brain Volume study is for people with MS who have been taking Tysabri for at least 2 years. With this study we will measure both clinical and MRI outcomes.  In terms of clinical outcomes, we will measure patient reported outcomes (PRO’s) which include questionnaires related to quality of life questionnaires, fatigue, functional capacity, as well as physical exams. In addition, we will do MRIs of the brain to measure patient’s brain volume. 

We will compare the patients’ outcomes with outcomes of healthy controls – people without MS, who are same ages and gender distribution as MS patients. We will evaluate two aspects:  a) whether there is any significant change in brain atrophy over a period of two years and b) how the rate of brain atrophy in patients on highly effective MS medication compares to the normal aging process in people without MS.

This is the first time that an MS study is looking at comparisons between MS patients and healthy controls. We are trying to understand whether or not the brain atrophy rate in patients who have MS that is controlled and who are receiving highly effective medications normalizes to the brain atrophy rate in the normal aging process.  Brain atrophy is a condition in which cells in the brain are lost, or the connections between them are damaged, resulting in decreased brain volume. 

How will this research add to what we already know about MS and brain atrophy?

There is a big gap in our understanding of whether if you can control the disease and brain atrophy with highly effective therapies. We don’t know whether the rate of brain atrophy in line with what we expect from normal aging, or if there is still increased brain atrophy despite the use of highly effective treatments. That will be the key question:  Can we confidently say that if we actively control the disease process through highly effective medications, the rate of brain volume change in MS patients is equal to someone without MS and normal aging process?

In the progression of MS research, why does this study important? 

We are trying to understand what interventions will maximize brain health. The key outcome in MRIs is that one of the stronger negative predictive values for MRIs for future disability is brain atrophy. If patients are losing brain volume, we know that is going to impact their disability over time, their quality of life and their overall brain health. Therefore, having an understanding of how you can positively impact brain atrophy rate is key.

What are the benefits of the medication as a longitudinal assessment of brain atrophy?  The fact that enrolled patients have been taking Tysabri for two years allows us to understand that whatever finding you have, you can assume that it’s due to treatment with Tysabri.

What would you say to someone who is thinking about participating in the study and why is their participation important?

We have a unique opportunity to understand how patients’ brain volume is changing over time. And the techniques that we’ll be using in the MRI’s are techniques that are not available in standard of care MRI’s, and insurance will not cover. So if you don’t have these MRI’s conducted in the context of research, you might not have access to that information.

This research will contribute to our understanding of the disease process. The patients will also become the population that will be the ideal outcome in terms of treatment. So if we can show patients that their disease is controlled with DMTs, lifestyle modifications, with exercise, and with activities that actually will maximize lifelong brain health, that will become a new model of care in which every patient should aim to get to that level. With this unique population of patients, we hope to demonstrate demonstrate that with a combination of highly effective drug therapies and other lifestyle strategies, you can maximize your brain health.

If you are interested in participating in this study, please contact Eric Engbretson with the RMMSC at Anschutz Medical Campus to find out if you qualify. Eric’s contact information is below:  Eric Engebretson
Professional Research Assistant
University of Colorado Denver
Office:  303-724-8388
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Flu Shots

Influenza, known to most of us as simply “the flu,” is a collection of viruses that typically cause well-known symptoms such as fever, aches, pains, cough, and stomach upset. It can sometimes be complicated by more troubling problems such as pneumonia. Influenza is a serious cause of death each year in the U.S., mostly in young children, the elderly, and those with severe chronic diseases, especially those that depress the immune system. 

With the imminent arrival of the flu season, questions and concerns regarding the flu vaccine are beginning to peak. Specifically, are people with MS at higher risk for the flu and should they receive the vaccine?  A SHORT COURSE IN VACCINES
Vaccines are developed against a variety of different disease-causing pathogens, including bacteria and viruses. There are at least three types of vaccines: whole virus/bacteria vaccines which are either inactivated (killed) or live but attenuated (weakened); and vaccines made with just parts of a virus or bacteria, typically part of the outer coat.

Most of the vaccines in common use for MS patients are the whole virus/bacteria type. Killed or inactivated virus vaccines are prepared by literally killing the pathogens (disease-producing agents) that make up the virus or bacteria. Although the virulent microorganisms are dead, they still possess the ability to provoke the immune system into producing antibodies and these protect the individual from the disease in question. Because the pathogens have been destroyed, killed vaccines do not, unlike live virus vaccines, have the potential to give the individual the disease produced by the pathogen virus or bacteria.

The other type of whole virus/bacteria vaccine uses “live” pathogens that are “attenuated”—or damaged—to make them made less virulent and harmful. This is often done by “passing” the strain multiple times, which means growing the virus repeatedly, selecting the strains that appear to cause less disease (perhaps in an animal model of the human disease), and thereby reducing its strength. Examples of live virus vaccines are the measles, mumps and rubella.

The typical Influenza A vaccines in common use in the last decade or longer have been available both as inactivated (flu shot) and live, attenuated (oral). In addition, for many years there has been available a live, attenuated vaccine, taken by mouth, which is also highly effective.

Although there were some initial concerns that the flu vaccine might provoke MS exacerbations, research does not support this. A 1993 study, headed by Dr. Aaron Miller of the National MS Society, found that among the 104 study participants there was no difference in the number of exacerbations experienced by those who received the flu vaccine and those on placebo. Other studies and extensive data collection have been undertaken as well and these have consistently found no link between relapses and the flu vaccine.

The flu shot, which is produced and distributed each year in order to protect individuals from the seasonal flu, is an example of an inactivated (killed) virus vaccine. For people with MS, the flu vaccine has proven to be a helpful tool for staying flu-free.

For these reasons, MS specialty doctors and the Center for Disease Control and Prevention (CDC) encourage MS patients to get the flu vaccine.

The Rocky Mountain MS Center and the National MS Society do not recommend the live attenuated vaccine for those with MS, and instead suggest use of the inactivated flu shot vaccine.



In the fight against multiple sclerosis, the Rocky Mountain MS Center is at the forefront of
developing improved treatments and a cure. With your support, we will continue our innovative work.
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Currently, the Rocky Mountain MS Center at Anschutz Medical Campus, co-led by the Rocky Mountain MS Center Medical Director Dr. Tim Vollmer and Dr. John Corboy, is one of the largest MS research programs in the U.S. Here are some ongoing projects I’d like to highlight:
  • There are 28 active clinical trials open, and more in the pipeline. Clinical trials include comparative effectiveness studies—meaning we look at the efficacy of one therapy against another—and outcome studies.
  • We can now process patients’ samples on-site, meaning lab work is done quickly and results are shared immediately with researchers. Thus the pace of research is accelerated.
  • Immunologist Dr. Leila Jackson heads up the translational research laboratory, which was officially launched this year. Dr. Jackson and her team, which includes two researchers, are laying the foundation for a "first in-man" trial of a complex vaccine approach to MS. This means we are actively moving toward a cure.
  • Dr. Jackson and her team are also developing a new animal model, used in early-stage studies, and have begun a new novel model involving the transfer of human cells from MS patients into immune-compromised mice—all in an effort to better understand the disease process. Other projects underway include looking into the role of B cells—both in therapy and their effect on the central nervous system (CNS)—and exploring the mechanism of action (how something works) of Copaxone and BG-12, the oral therapy under investigation. 
  • Additionally, we are collaborating with Stanford University on studying the potential cause of MS in relation to a protein found in foods. We are thrilled to be partnering with such an outstanding academic institution.
With your support we can do what we all dream of—discover a cure.

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