In this full-length doctor's interview, Ben Thrower, M.D., explains how a new drug may be able to slow the progression of Multiple Sclerosis
December 15, 2003
Ivanhoe Broadcast News
Ivanhoe Broadcast News Transcript with Ben Thrower, M.D., Neurologist, The Shepherd Center, Atlanta, Georgia
Whatís the idea behind your Multiple Sclerosis research?
Dr. Thrower: [The drug NBI-5788 consists of] an altered peptide ligand, and the idea is that rather than trying to suppress the immune system to treat multiple sclerosis, youíre trying to actually take advantage of a natural response that our immune system has. The altered peptide ligand looks a little bit like one of the natural components of the covering of nerve fibers in our brain and spinal cord, something called myelin basic protein. The idea is that the altered peptide ligand will look like myelin basic protein, it will interact with immature white blood cells in our immune system, and actually rather than letting them develop into an aggressive or attacking sort of white blood cell, it will send them down the pathway to being a more regulatory, more protective type of white blood cell.
What does that translate into for the patient?
Dr. Thrower: Hopefully, what it will translate into are fewer MS attacks, no progression of disability, and an MRI that looks stable or better over time.
Is it just for patient in advanced stages?
Dr. Thrower: We donít know with any of our new drugs, ultimately, what types of MS they will be used in, but for a study, you have to pick one particular type. The type of MS that this drug is looking at initially will be people with a very aggressive, inflammatory form of MS. More likely than not, they will be people who are relatively newly diagnosed who have a pretty aggressive up-and-down course to their MS, with an MRI that shows some active inflammation.
What were the results from the first trial?
Dr. Thrower: In the initial trials, what weíve seen is that the drug appears to be safe and it appears to suppress the inflammatory activity on MRI.
So, this trial will be taking it a step further to look at the safety of the drug in a larger group of people and again, to look for evidence that weíre suppressing that active inflammation on MRI.
Talk about the lesions. Was there a reduction of lesions?
Dr. Thrower: Correct. When we look at lesions on MRI, we talk about lesions that are either actively inflamed or what we call a T2 lesion, which is a lesion that may or may not show active inflammation. What weíve seen so far with the studies, with altered peptide ligand, is that it appears that both of those are suppressed over time.
Is NBI-5788 a new drug?
Dr. Thrower: The only application for the altered peptide ligand has been for multiple sclerosis. The idea of using this goes back a few years, but it really is unique to multiple sclerosis.
How is this study different from the other studies looking at NBI-5788?
Dr. Thrower: This is going to be a larger study. Itís a multinational trial primarily based in the United States and Canada, but it will be the first multicenter trial, rather than just focusing on one center with a small group of people with MS. This will be at multiple centers with a large number of people with MS, which should give us a better feeling for its safety and effectiveness.
Based on earlier trials, are there any side effects of taking NBI-5788?
Dr. Thrower: We donít worry too much about side effects. One thing that weíll have to be careful about would be any sort of hypersensitivity reactions with the drug. When weíre altering the immune system, not really suppressing it but sending it down a pathway, thereís a balance in our immune system between these inflammatory types of cells and these more regulatory types of cells. The more regulatory type of white blood cells also carries with them a little bit of potential for allergies. We think these types of white blood cells are the ones that may regulate whether someone has, say, hay fever and things like that, so they also may carry with them a little bit of risk of skin reactions, hives and side effects like that.
How is it administered?
Dr. Thrower: The altered peptide ligand that weíre going to be looking at is given by a subcutaneous injection, so itís given just under the skin. The way that the drug will be administered is with a weekly dose up front for five weeks and then it will shift over to just a once monthly dose. One of the things thatís so exciting about this is that if it worked out, itís so much more convenient than some of the things we have right now.
How is this treatment different from standard treatment?
Dr. Thrower: We think that the altered peptide ligand would have several potential advantages. First would be that itís probably more specific in treating MS. Weíve really gone from an era pre-1993 of just suppressing the immune system or sort of taking a sledge hammer and beating the immune system into submission. Then in 1993, we had the first of a class of drugs called immune modulators, drugs that really fine-tuned the immune system and tried to tone things down. I think what the altered peptide ligand would represent is an even more specific way of doing that. Right now, all of our medications are given by injection ranging from once a week to every other day to one thatís three times weekly, one thatís given every day. The altered peptide ligand in this trial is going to be given weekly for the first five weeks, and then it would be given by subcutaneous injection once a month, so just from a convenience standpoint, it would represent a big improvement.
Why is this being considered a breakthrough?
Dr. Thrower: The altered peptide ligand I think would be considered a breakthrough because again, itís just another step forward in how specifically we can fine-tune the immune system in a person with multiple sclerosis. The other reason that it could be a breakthrough, and this may be further down the line in terms of getting information on this, is this pathway for working with the immune system has the possibility for being used outside of multiple sclerosis. There is a suggestion that when you modulate the immune system, you send the immune system toward itís more protective sort of white blood cell, that that more protective white blood cell may actually make some things in the brain and central nervous system that can lend these sorts of medications to being used outside of MS, things like Parkinsonís disease or Lou Gehrigís disease. Again, we donít know that yet, and itís down the line, but weíre starting to see the MS research overlap a lot with spinal cord research and research into neurodegenerative conditions like Parkinsonís disease.
What were some of the benefits that you saw when using NBI-5788?
Dr. Thrower: The benefits that we saw from the earlier trials
were that it appeared to be a well-tolerated mediation, it was easy to
give in a once-monthly dose, it suppressed the MRI activity, mainly in
the form of active inflammation. The trials were not designed specifically
to look at things like relapse rates and progression of disability, but
that would be the hope also is that it doesnít just make the MRI look better,
but that it actually slows down the clinical activity of someoneís multiple
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