Stanley Iyadurai, PhD, MD, Assistant Professor of Neurology with Specialization in Neuromuscular Medicine and Neuromuscular Clinical Pathology at The Ohio State University Wexner Medical Center in Columbus, Ohio talks about a new drug for patients with CMS.
Interview conducted by Ivanhoe Broadcast News in April 2017.
I wanted to start by asking you about CMS, what that stands for and essentially what it is.
Dr. Iyadurai: CMS stands for Congenital Myasthenic Syndrome. By description, congenital means from birth and myasthenic means type of weakness. It is named that way partly because it mimics Myasthenic Gravis which is also a condition that causes weakness, but associated with antibodies that have genetics in certain proteins of the body. In Congenital Myasthenic Syndrome there are no antibodies, but they have very similar patterns of weakness as can be seen in Myasthenic Gravis which is a more common condition.
I wanted to ask about patient symptoms, do they start vague, and is it hard to get a diagnosis?
Dr. Iyadurai: Yeah, the symptoms can be very vague; it can be as simple as fatigue. If you think about it, fifty thousands of people are going to have fatigue. But what makes this different is in the setting of fatigue they may also have eyelid dropping, they may have difficulty swallowing, and they may have difficulty breathing. These may just come and go, they may be intermittent, they can be just present here and there. Or sometimes they will notice only when they have done a lot of work.
How severe can this be, does it have different stages?
Dr. Iyadurai: In some people it may be less severe as much as somebody may not ever notice this for tens of years. It may be a very subtle eye droop on one side that may have just persisted forever. Or in some cases it can be bad enough that they have to be intubated and admitted to ICU. And in some cases it may be of such nature that they may not be able to move around at all and they may have difficulty swallowing as well.
Is this a genetic condition?
Dr. Iyadurai: Yes. Congenital Myasthenic Syndrome would be genetic condition.
What are the concerns then if you have a family?
Dr. Iyadurai: Most of the Congenital Myasthenic Syndromes as described so far out of the thirty genes that cause Congenital Myasthenic Syndrome the majority of them, when I say that it’s about close to twenty six or twenty seven of them, are recessive in nature, which means you need two bad copies to show the disease. Therefore if children are involved, in most cases if the parents are affected, one of the parents is affected, the children are almost always not affected.
What are the treatments?
Dr. Iyadurai: There are a couple of treatments and this work has been mostly spearheaded by the Mayo Clinic from the seventies and eighties. One most common medication that’s used in this condition is called peridostigme or mestestnon as the trademark. It’s a similar medication that’s also used in Myasthenia Gravis, it helps that condition as well. However there are many different types of it out there and some of them can be made worse with pynidostigmine. And in those conditions you’re to try several other ones. There are other agents as 34BAP, there is ephedrine, there is albuterol, there is fluoxetine and some other agents that have been experimentally tried and in some cases they have been beneficial. But to know exactly what would be helping them you need to know what type of Congenital Myasthenic Syndrome they have.
I wanted to ask a couple of questions about LEMS, another condition that many of our viewers probably haven’t heard of.
Dr. Iyadurai: LEMS stands for Eaton-Lambert Myasthenic Syndrome. It’s a condition that also mimics Myasthenia Gravis in a general sense with eyelid drooping and certain difficulties with eating and swallowing. And maybe even difficulty with breathing. But it’s associated with an antibody that’s usually not associated with Myasthenic Gravis, under the condition in most cases it’s associated with small cell lung cancer. The antibodies generated against educated calcium channels cause LEMS.
In terms of a treatment for the two is there a new clinical trial that’s undergoing?
Dr. Iyadurai: For the treatment of Congenital Myasthenic Syndrome and LEMS there is a company out there which has a product called 34DAP that is currently being tested for the clinical efficacy to see if that can be used as the mainstay treatment.
What would that do, what differences are a patient on this clinical drug feeling that the old drugs aren’t doing?
Dr. Iyadurai: In terms of treatment outcomes, which is the same response that we expect to see in patients, we expect their eyelid droop to become completely normal, their speech to become completely normal, their swallowing difficulties go away and the fatigue gets better. However, this is not a medicine that will work for everybody, but in the classical cases a subset of Congenital Myasthenic Syndrome patients will definitely benefit from this drug.
In your mind could you describe what it is like when you’re dealing with patients who have one of these rare diseases that is just so difficult to pinpoint and then tough to treat.
Dr. Iyadurai: If you don’t know what you’re dealing with there is no way you’re going to treat them. If you start throwing medications at them it’s like shooting in the dark. So you need to have absolute specific way you can diagnose this condition. This might require very detailed electro diagnostic testing, so called preparative none stimulation testing, and blood work that may be necessary in addition to a specific DNA-based gene testing. There are certain clues that may come from patient’s history, patient’s clinical course and how they progress over time, how they did as a kid. Physicians can usually pick up these clues and come up with a tentative diagnosis and then go on to further characterize them electro diagnostically, and finally gene test to show whether or not they have that condition. Once you know the condition, then there are options for treatment and some of those have been fairly well defined. In some cases it’s a method of trial and error.
How common is it in the United States, both CMS and LEMS?
Dr. Iyadurai: Both CMS and LEMS are rare disorders, and the incidence is not exactly known but literature does suggest that it is two to three in hundred thousand. If you look at cases that are being identified more and more one would probably say that these are under-diagnosed patients and there is probably more people who are affected that are not being diagnosed at this point.
How important is it to have this new drug for you as a clinician treating these patients?
Dr. Iyadurai: Any additional treatment option that’s available is another tool in the armamentarium. So to have another medication that would be helpful in treating at least a subset of Congenital Myasthenic Syndrome or LEMS would be extremely helpful. In some cases the medications that work may lose efficacy with time. In those cases, this can be used as an adjunct medication to add on to a prior medication.
If there was one takeaway that you would want our viewers to know about this medication, about the clinical trial what would that be?
Dr. Iyadurai: The clinical trial is listed to pick up the efficacy of the medication in terms of treatment. And this is a rare disorder so if people are interested in being part of this study they should make that known so that they can get them associated with a coordinator so that they can be included in the trials. And this is because it’s a rare disorder maybe we’ll have fewer numbers, but having shown efficacy in smaller numbers will allow us to do larger trials and then treat people in a bigger context.
Is there anything I didn’t ask you that you want to make sure people know?
Dr. Iyadurai: I think if there is a question of fluctuating symptoms or if its fatigue, the patients have to be persistent in finding a provider that will address these issues and then maybe in medication trials it may be necessary to make diagnosis. But ultimately I think DNA-based gene testing would be the way to diagnosis these conditions and one has to be persistent and patient to get there.
Your patient Elaine, she had mentioned that you knew by looking at her eyes. Can you tell me how?
Dr. Iyadurai: These are the clues that we talked about that could be picked up on examination on observation. Maybe neurologists are more attuned to looking at these conditions but when I looked at her first there was something called atosis which is the medical term for eyelid droop. And it was first noticed on her left eye and within two minutes of talking the fluctuation of the eyelid drop went to her right eye and the left eye became normal. So whenever this type of fluctuating atosis that happened I knew this must be Congenital Myasthenic Syndrome.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Dr. Stanley Iyadurai
614-293-4969
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