Here are selected questions from an FSH Society webinar held on October 1, 2015, with Rabi Tawil, MD, co-director of the MDA Neuromuscular Disease Clinic at the University of Rochester, New York, and lead author of the first evidence-based care guideline for FSHD, a project the FSH Society supported through consultations and advocacy. Summaries of the guideline can be downloaded here.
TAWIL: FSHD is a relatively rare disorder, and because of that, it’s difficult to come up with evidence-based guidelines. Evidence-based means that you go through the literature, and there are a lot of papers that you can use for evidence for certain approaches to taking care of patients with FSH muscular dystrophy. So as a consequence of FSHD being a relatively rare disorder, there are only a few physicians who have experience in caring for individuals with FSHD. Even general neurologists, and even more so, primary care physicians, have little or no knowledge of this disorder and how to take care of patients with FSHD.
To write the evidence-based guideline, we first gathered the evidence, reviewed all the literature that has been written about FSHD, decided what are the most important clinical questions that we need to address and limited ourselves to where there is evidence, analyzed the evidence, and then provided practice recommendations based on this evidence.
A literature search found 977 abstracts of journal articles. There were very strict criteria to consider good evidence. The 977 abstracts were narrowed down to 176 articles that we thought contained good evidence that we can look at.
Q: I would like to get your thoughts on physical activity for young adults who have been diagnosed. Are they better off staying highly physically active, more specifically, doing weight training, or should they try to conserve their muscle strength?
TAWIL: There’s increasing evidence that aerobic exercise is good and makes people who have FSHD feel better. They are more active and more physically fit because of it. Now, obviously, there’s a certain breakpoint; if somebody is very weak, then they have limited capacity to do certain types of exercises, so it’s kind of a combination of remaining as active as possible without draining yourself so much that you cannot go through the whole day. And this is why it’s really important to not go out on your own, but actually seek the help of a physical therapist and work closely with them to see what is the most appropriate type of exercise for you to do. And, again, that’s just aerobic exercise. Weight training should not be the type of weight training to build muscle, but more with light weights, because if you apply resistance or heavy weights, depending on how affected you are, you may get some overuse injuries to your shoulder, for example, just because you’re overdoing it. Everybody has to remember that their joints are only as good as the muscle around them. If your muscles around your shoulders or your knees, for example, are not very good, you have to be very careful about weight training.
Q: Why is FSHD2 genetic testing not readily available, and what makes it so difficult to diagnose?
TAWIL: There are several levels of testing that you have to do, and it was really developed all in one lab. Most of the data were generated from one lab in Holland, and it’s a very tedious process, but I’m happy to say that the University of Iowa Lab is now offering FSHD2 testing.
Q: I am wondering if you are aware of any advances in the treatment for FSHD?
TAWIL: Yes, since doctors have figured out that the expression of DUX4 in muscles is what causes FSHD, there’s a lot being done on treatment, and I can tell you, five years ago, no drug company was interested in FSHD; now there are many drug companies working on treatments. Ultimately, the best treatment is going to be something that targets the source. If there’s a way of turning off DUX4, that would lead to stopping FSHD, basically, and potentially reversing it.
But there are other approaches that you can take also to treating some of what we call the downstream effects of DUX4 expression in muscles. There’s a company called aTyr that’s now looking at a very new product that they’re developing that’s anti-inflammatory and they think—and we know—that at any one time, patients with FSHD have inflammation in one or more muscles, and this company is doing a study right now. There are several sites in Europe. There are two sites in the US, including our medical center and Ohio State University in Columbus.
They’re looking for very specific patients to do this on, and so what they will do is scan somebody with an MRI, and based on the appearance of the MRI, if there’s an indication that any one muscle is inflamed, then that person would qualify for the study. This is an early-phase study. The treatment is given intravenously once a week, and they will repeat the MRI, and if evidence of inflammation goes away, then it means that their medication is doing what it’s supposed to do. Then, if they’re successful in this early-phase study, they’ll do a second study that goes on for a longer period of time, and then they will determine if turning off the inflammation actually helps prevent the muscles from getting worse.
Q: The anti-inflammatory process that you’re looking at now under the current study: Is there any information about the effect of some of the other biologics such as Humira, when taken for other conditions, on FSHD?
TAWIL: No, there is not. And this is a very good question. I think one of the issues has been that we really don’t know whether the inflammation is a primary thing or a kind of byproduct of the muscle fiber destruction. Many years ago we did a trial with prednisone, which is not a very specific anti-inflammatory, but it’s a very powerful one nonetheless, and we did it in 15 patients; we gave them high doses for three months, and there was no difference in their strength, and, actually, the only thing that happened is that they gained a lot of weight. But it is a good question. Could it be that a more targeted new biologic—would it be useful for FSHD? I don’t know. I’m on the fence as to being certain that treating inflammation is really going to make a difference as opposed to it being just a byproduct of the underlying dystrophy. You know you don’t want to go in with a big hammer that can cause a lot of side effects, when you’re not certain about what can happen. I think, to me, what’s interesting in the aTyr trial was that their product actually seems to be very safe and very well tolerated, and in the lab experiments that they’ve done, it seems to be a fairly powerful anti-inflammatory. Again, it’s kind of a risk/benefit question, and I thought there was not a lot of risk to it, and it’s worthwhile trying.
Q: I need more sleep than the average person. I seem to fatigue faster than my cohorts. Is this common with FSHD?
TAWIL: I think this is common—this is common in really all of the muscular dystrophies, and it has to do oftentimes with the increased energy that somebody with FSHD has to put out to achieve a normal amount of walking or climbing stairs. But the other thing is to make sure that there’s no other issues that are causing fatigue. Fatigue can be caused by many things, and one of the commonest is problems with sleep, and so again, this is one of the things that physicians should be asking their patients. If somebody’s predisposed, if they have a lung capacity that’s reduced, they may not have any problems when they’re sitting up, but when they lie down, their lung capacity is smaller because they don’t have gravity helping expand their lungs. And they may have nighttime hypoventilation, meaning that they are not getting rid of their carbon dioxide, and they wake up fatigued in the morning. This is something that needs to be looked into as a potential cause for daytime fatigue.
Reference: Evidence-based Guideline: Evaluation, Diagnosis, and Management of Facioscapulohumeral Muscular Dystrophy, a report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the Practice Issues Review Panel of the American Association of Neuromuscular & Electrodiagnostic Medicine.
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