MS Under a Microscope - Up-to-the-Minute Research

A funny thing happened on the way to San Francisco. ABILITY editor-in-chief Chet Cooper planned to fly up from LAX for a few hours to meet with one of the foremost authorities on multiple sclerosis: Dr. Douglas S. Goodin. But it turned out Cooper was grounded.

“May I have your attention, please?” a voice came over the P.A. system as he sat in the boarding area. “Flight 293 to San Francisco has been cancelled.” That was followed by more good news: “There are no more flights to San Francisco today.”

After a few passengers had full-on tantrums, the airline put them on the local, flying them into San Jose, and then shuttle-busing them through Palo Alto and San Mateo up to San Francisco, 45 minutes away.

It was a bumper to bumper ride. But all was not lost. As sometimes happens, Cooper got a good seatmate: Melanie Jameson. He told her he was in town to talk with neurologists at UCSF’s Multiple Sclerosis Center. “What a weird coincidence,” she replied. “I have MS myself!” She’d recently relocated from New York to Northern California, and had yet to find a local doctor. So he took her along to the interview. Her questions would be as good as his own, if not better, he reasoned. Jameson would bring a patient’s perspective to the conversation about the causes, treatment, and possible cures of MS, which affects roughly 400,000 people in the United States.

Chet Cooper: How would you describe MS?

Dr. Goodin: MS is an inflammatory disorder of the nervous system that tends to occur in episodes. So people get symptoms of neurologic dysfunction: blindness, numbness, weakness, imbalance, trouble with bowel and bladder. It lasts for a period of weeks to months and they typically remit at the beginning, and then later on, over the course of the illness, many patients experience a more steady and insidious progression of their disability, which is where we call the transition from remitting/relapsing MS to secondary progressive MS. A few people, not very many, have progressive MS right from the get-go. But by and large, we think of MS as being these recurrent inflammatory episodes that affect the brain in a relatively random way.

CC: How would a doctor evaluate someone’s symptoms and diagnose MS? There are a lot of symptoms that could be due to something else.

DG: Well, potentially, any symptom in the nervous system could be due to MS. As I said, it could be blindness, numbness, weakness, a whole variety of things. The key to making a diagnosis is that usually MS patients are young, the typical age of onset is between the ages of 20 and 40, so that takes it away from some of the other diseases of the nervous system, like strokes, which tend to affect an older age group. So if a person comes in and they’re young, it’s more likely that you’re dealing with something like MS. This recurrence and then remission, that pattern of illness, is very characteristic of MS. If a person comes in with that, that ought to at least be on your mind. We’re obviously also helped out by laboratory tests, MR scans. Now we can image the person’s brain and actually get a very clear picture of what is going on in their central nervous system. Similarly, spinal fluid can provide us with information that would not be present in some of the other neurological problems.

CC: Can you take us through a little bit of the standard procedure for treating MS?

DG: It’s not usually that the person has been suffering from something or having symptoms for years. They come in with these episodes, so they may come in with an episode where they, for instance, can’t see out of their left eye, or they can see very little out of their left eye, and it’s come on over the course of a week, and now they’re coming to us and asking our opinion or asking for treatment, or both. And then we will take a history and say, “Have you ever had anything like this before?” And they’ll say, “Well, there was that one time in college 20 years ago or 10 years ago or five years ago when I woke up in the morning and my whole left side had gone to sleep. I couldn’t feel anything in my arm or leg. It was there for a week and it went away. I was told by the doctors that it was stress and finals. I didn’t think anything more about it.” That would be an important event for us to know about that would help us make the diagnosis of MS. But usually, in the interim they have not had any problems. They usually will be functionally normal.

CC: What’s your opinion of the typical drugs used to treat MS? Avonex, Betaseron, Copaxone—the “ABC” drugs.

DG: Well, I think all of us have our own take on the ABC drugs—which ones are more effective, or less effective. My own view is that the interferons as a class, of which there are three, Avonex (Biogen), Betaseron (Berlex), and Rebif (Serono), have better evidence of being effective than Copaxone (Teva). That doesn’t mean that Copaxone doesn’t work as well, it just means that it hasn’t been studied as thoroughly, so I have less confidence. That makes me use Copaxone relatively less. Other people are impressed by the fact, and it’s certainly true, that Copaxone is very well-tolerated and, in fact, is probably better tolerated than the interferons. They’re not as disturbed by the fact that there’s less evidence of it being effective, they like the side-effect profile and they’re more likely to use Copaxone. I think there’s a lot of individual physician variability on that.

CC: Can you tell me about the trials that you’re doing at UCSF?

DG: UCSF is actually involved in a lot of trials. One of the trials that I’m doing is looking at Betaseron, which is one of the interferons, in its current dose, doubling the dose and comparing it to Copaxone. That trial’s actually almost over. We’re about to take on a couple of trials with some novel agents that are not currently approved by the FDA but have very promising results in phase two. One of them has the very catchy name of FTY720, which just rolls off your tongue. I think it will have another name when it’s marketed, though.

FTY720 looks very promising in phase two, and it’s an oral treatment, so it would avoid the injection, so that would be great. There’s another one that is called Rituximab (Genentech), which is also being used as an anti-cancer drug, so we have some information on the safety of that. The nice thing about Rituximab is that it also has great phase two data, but the really nice thing is, you only inject it once every nine months to a year. So both those drugs, if they work, which I hope they will, will actually be a major step forward.

Melanie Jameson: How do these two drugs compare to Tysabri?

DG: Tysabri (Biogen) has some problems, because of the two people that got a rare, usually fatal brain infection called multifocal leukoencephalopathy during the study. That’s made some people a little nervous. The idea of putting a 22-year old on a drug that could kill him doesn’t sound like a good choice. [i](laughs)[i] So it’s going to be two or three years before I’m going to feel really comfortable with Tysabri’s safety profile.

By that time, I think these other two drugs are going to be on the market. It’s usually very hard to know in phase two how they’re going to look in phase three. One of the things that was really impressive with Tysabri was that the phase two study was a big study—involving almost 200 patients—and gave us a really good clue as to what we were going to see in phase three.

The same size study has been done on these two new drugs, and they have, at least in phase two, similar efficacy to Tysabri. But they probably have a better side-effect profile. In other words, FYT720 has actually been used in kidney transplants, so we have a fair amount of at least short-term data on FTY720, and Rituximab’s currently FDA approved for treatment of some cancers, whereas with Tysabri we really didn’t know. It was brand new. But we’ll see. Both of the drugs are very potent. I mean, the fact that you only have to use Rituximab once every nine months means that it works for a long time. There’s no take-backs. You can’t go, “Oops!”....Continued in ABILITY Magazine

www.ucsf.edu/msc

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