Interview With Dr. Nazli McDonnell, Part 1

— -- This is an unedited, complete transcript of ABC's interview with Dr. Nazli McDonnell.

OFF CAMERA COMMENTS]

INTERVIEWER

All right, so, [CLEARS THROAT] the first one is the obvious one, I mean if you can give us just a very…simplified, concise definition of what this mysterious EDS is.

DR. NAZLI McDONNELL

EDS, Ehlors-Danlos syndrome, is a disorder of the connective tissue, which includes the joints, the skin, and sometimes the blood vessels.

INTERVIEWER

But why is it so mysterious?

DR. NAZLI McDONNELL

It's mysterious because it's often missed. That's because the patients who have EDS look just like any other normal person, average person, when you look at them. But the defect is in their skin…because if they injure their skin it can take a long time to heal.If they scar it can become a very abnormal, big scar. Their joints look normal to look at, but they can dislocate, and they have a huge amount of pain associated with the joints. And the blood vessels, they…they're in the right places, but they can be more fragile than normal persons' blood vessels.

INTERVIEWER

Well…one of the things that…uh, one of the symptoms that is, is most obvious, is the stretchy skin, the, um…Tell me about that, that is so mysterious, that is such a…an enigma.

DR. NAZLI McDONNELL

The reason, uh, that the patients with EDS have stretchy skin is that the collagen found in their skin is abnormal. Therefore when you stretch it, it can -- it can stretch out, way past a normal person's skin. And for that reason in the old days, patients with EDS were often in circuses, showing off their stretchy skin.

[OFF CAMERA COMMENTS]

DR. NAZLI McDONNELL

It is mysterious to the doctors because, um…it is the same reason that it's mysterious to everybody else, the people who have EDS look just like a normal person. And often they present to the doctor, complaining of joint pain or that they have scars that are big and ugly…Maybe we should redo that one [LAUGHS]. I don't wanna say ugly. Uh, the, uh, the reason, um… EDS is mysterious to the doctors is for a number of, um…causes, and, uh, one of them is that, people with EDS look like just any other person to look at. And second of all, it's rare. Therefore the doctors may have heard about it in medical school but they have never encountered a person with it so it goes to the back of their mind and they don't recall it. Um…the patients with EDS often go to the doctor complaining of joint pain. And joint pain has many causes and it's not on the top of the doctor's list that the patient may have EDS. Therefore it gets often missed.

INTERVIEWER

Uh, why do so few people know about it? About EDS.

DR. NAZLI McDONNELL

Because it's a rare disorder. Um, it affects about, um, maybe one in 5000 to one in 10,000 persons. But we estimate that only about 10 percent of those who are effected have been diagnosed.

INTERVIEWER

That's amazing to me. All right, how can it be that only 10 percent of those who have it are diagnosed?

DR. NAZLI McDONNELL

There are several reasons for that also.

INTERVIEWER

Uh, could you repeat the question, there's several reasons for what, you know --

DR. NAZLI McDONNELL

There are several reasons for the low, uh, rate of diagnosis, for affected individuals. Um, one of them is that the disease is itself quite variable. [12:07:30:18] So there might be more than one person affected in a family with the same genetic disorder, but, one of them has severe manifestations, severe symptoms, and the next person who might have the same gene, is not affected so much. The symptoms are better controlled. T 27 [12:07:49:01] Uh, so the range is from mild to severe, and the patients who are more severe tend to be diagnosed. The ones who are milder tend to be missed. Um, the second reason why the rate of diagnosis is so low is that, um, many physicians are not aware of the disorder, they had only heard about it in medical school and had never diagnosed someone themselves. [12:08:16:01] Um, in addition, the disorder presents itself often in teenage or adulthood. It's not often noticed in childhood. And typically pediatric doctors, the children's doctors are more tuned in to genetic disorders. And adult doctors are not tuned in to diagnosing genetic disorders.

INTERVIEWER

[12:08:39:01] But, it may be rare but it's not new, I mean, uh, it's been described all the way back to Hi -- uh, Hippocrates I believe described…

DR. NAZLI McDONNELL

T 27 [12:08:48:22] There are, uh, reports of diag -- diagnosis of an EDS-like disorder dating back to the Greeks. But the formal, um, description of the disorder happened around 1899 -- 1899.

[OFF CAMERA COMMENTS]

DR. NAZLI McDONNELL

[12:09:13:12] Um…EDS has been described as, uh, far back as the Greek, but the formal diagnosis, um, and description happened around 1899 by a Danish dermatologist.

INTERVIEWER

But 1899 is a very long time ago.

DR. NAZLI McDONNELL

[12:09:30:13] Yes.

INTERVIEWER

I mean, it -- that makes it an old disease in my mind.

DR. NAZLI McDONNELL

Yes, it is an old disease, and human genetic diseases are all old. That means they're built into our genes and there has been examples of that…uh, since the origin of humanity. [12:09:47:20] But, the description and understanding of these disorders has come much later. Uh, what has happened about EDS in the last 15 or 20 years is the, um, identification of the genes that cause it. And that has raised awareness as well as improved the diagnosis.

INTERVIEWER

[12:10:08:13] Um…we -- you mentioned that, uh&30133ome families that carry the genes have different manifestations, some mild and some very severe. We talked last week with a mother and a son who both have been diagnosed with the disease. [12:10:24:25] The son is only 19 years old, and he's confined to a wheelchair. The mother has a…very mild case, wears braces on her arms. Talk to me about how…rare -- I mean, how…how often does it happen that it can hit a 19-year-old so hard? [PAUSE] Is this a common ex -- is this is a common…

DR. NAZLI McDONNELL

[12:10:55:01] [PAUSE] It is rather uncommon for a young person to be severely affected with EDS. Uh, but it has happened. And we have seen examples, uh, where, uh, a parent also carries, uh, the disorder but has mild manifestations. However, um, there is a, uh, younger person, a son or a daughter, who has severe manifestations, and it's -- Although rarely it has happened that, um, it's so severe, that the person is wheelchair-bound at a fairly young age.

INTERVIEWER

[12:11:31:21] Well I mean that's what I really wanna get at because the young man that we talked with, um, is in severe pain, um, and heavy pain medication, and, uh, is wheelchair… dependent, if not wheelchair-bound, uh…How rare a case is that?

DR. NAZLI McDONNELL

[12:11:51:09] It's fairly rare that a person is wheelchair-po -- bound or requiring, um, narcotic pain medications in teenage years or young adulthood, but it has happened. Um…part of the focus of this study here at the National Institutes of Health is that we are trying to understand the different manifestations in different members of the same family. [12:12:16:12] We think that there are some genes that modify the expression of the disease. And if we can identify those perhaps we can have an insight into how to treat the complications of the disease.

INTERVIEWER

How far along are you?

DR. NAZLI McDONNELL

[12:12:30:21] We have made some progress.

INTERVIEWER

Uh, how far into your study are you?

DR. NAZLI McDONNELL

Uh, we've been recording participants, uh, for the last three years. There was a prior study at the, um…um, at NHGRI.

[OFF CAMERA COMMENTS]

DR. NAZLI McDONNELL

[12:13:00:29] Um, there was a prior study at the National Human Genome Research Institute, uh, where several, uh, patients were seen as well, with this disorder. And, um, we've been continuing on that work. Um, we have enrolled about, um, 200 patients with various forms of EDS.

INTERVIEWER

[12:13:21:29] What does happen to the genes?

DR. NAZLI McDONNELL

[12:13:25:23] The patients with, um, EDS have a mutation, in one of the collagen genes. Meaning that there's a spelling error…in the gene that codes for the collagen. Therefore the collagen that's produced by the fibroblasts, and the, um…cells in that person, make the abnormal form of collagen, instead of the normal form of collagen. And the confers weakness to the, uh, skin and the joints and the blood vessels.

INTERVIEWER

[12:14:01:11] All right, you're gonna show us -- what are you gonna show us on the microscope in a little while?

DR. NAZLI McDONNELL

I'm going to show you the fibroblasts, meaning the skin cells that we have grown in a, uh, dish, from a patient with EDS.

INTERVIEWER

Okay.

DR. NAZLI McDONNELL

[12:14:17:11] And from the fibroblasts we can extract the collagens and study them, trying to understand what's happening with that patient.

INTERVIEWER

If you get a cure, are you anywhere near a cure or a treatment for this?

DR. NAZLI McDONNELL

[12:14:32:03] We're not near a cure or a treatment per se. But we're -- we've made headway into understanding all the complications of the disorder, so that we can address the symptoms. We're also looking at some new strategies into how to treat the disease. But those are in the early stages yet.

INTERVIEWER

T 27[12:14:52:27] What, what kind of new strategies?

DR. NAZLI McDONNELL

The new strategi -- strategies include, uh, trial with medications that can increase collagen production. It can also include some genetic strategies to shut down the abnormal copy of the gene. But that's, is going to be in the years to come.

INTERVIEWER

[12:15:16:05] Years, not…are you -- when you say years are you talking decades or…how many years. I mean --

DR. NAZLI McDONNELL

I think --

INTERVIEWER

-- I know you can't give a, an exact --

DR. NAZLI McDONNELL

[12:15:23:27] No, I -- I think in the next decade, we'll have, um, some approaches that are going to be successful.

INTERVIEWER

[12:15:32:15] If you get a…a cure, or some kind of treatment for EDS, how -- I mean EDS is very rare, so it will affect just a few peo -- some -- you know, the people who have it, but, how would that be applicable to the rest of us, say for like arthritis or other disorders, is there, is there a way that the research that you're doing on EDS can be applied to the larger population?

DR. NAZLI McDONNELL

[12:16:04:08] Yes. The, um, patients with EDS, can be seen as…persons who age prematurely in terms of their skin and joints. We see an incidence of arthritis at a much earlier age than the general population. The typical EDS'er develops arthritis in their thirties and forties as opposed to their fifties and sixties in the general population. [12:16:32:19] So we are hoping that the treatment approaches we develop for EDS will be applicable for the treatment of, joint and skin complications in the general population.

[OFF CAMERA COMMENTS]

INTERVIEWER

[12:17:03:20] I am trying to get at -- and I thought this was a very good answer, um, that, um, uh, the, um…you know…if the research you're doing for this rare disorder --

DR. NAZLI McDONNELL

Mm-hmm.

INTERVIEWER

-- can have --

DR. NAZLI McDONNELL

[12:17:16:00] Generalized applications.

INTERVIEWER

Yes.

DR. NAZLI McDONNELL

[12:17:18:15] Yes, and that is why ge -- the National Institute on Aging has invested in this study, so that we can understand more, using the rare disorders as a focus of investigation, but having applications to the treatment of disorders that affect the… population that is aging in general.

[OFF CAMERA COMMENTS] DR. NAZLI McDONNELL

[12:18:10:28] The reason National Institute on Aging has invested in this study is that we are using EDS and other rare connective-tissue disorders as a tool to understand the disorders that affect the general aging population, such as arthritis, poor wound healing, and fragility of the blood vessels.