Gene Therapy: For Reverend Wilson, A Blessing – angina patient Charles Wilson – Interview
Could his case be a watershed moment in the annals of cardiovascular surgery?
Gene therapy was the only hope left for the Reverend Charles Wilson. When he got on the Internet and met some researchers, he successfully changed his dismal prognosis.
Reverend Wilson knows more about genetics than just who begat whom in the Bible. He knows all about the genes that have caused cholesterol-filled blood vessels to bring early deaths to his loved ones. His grandfather died from a heart attack at age 39. His mother died after cardiac bypass at the age of 60. Six of his aunts and uncles died from heart disease. He is one of four siblings, all of whom also have heart disease. Three of his six children had cholesterol readings of 350 or more in early childhood.
Small wonder that his cardiologists told him they could do no more for him after two bypass surgeries and numerous angioplasties.
“You will have to go home and wait for technology to catch up with you,” they told him.
Being a person of unusually strong faith and optimism, Charles Wilson did not go home to die, even though he could only walk a few minutes before running out of breath and just getting out of bed to dress was an ordeal.
Modern medical surgeries–revascularization of the blood vessels of the heart–were no longer going to help him. The veins in his leg and a mammary vein had already been used for bypasses. But the interesting thing about Charles Wilson’s success story is that technology had caught up with him, and just in time.
Could his case be a watershed moment in the annals of cardiovascular surgery? Our thoughts go back to an American Heart Association convention in 1989. No planner could have anticipated the throngs of cardiovascular surgeons who jammed the seminars where the then relatively new advances in bypass surgeries were being explained.
While other conference rooms were relatively unattended, the rush to learn about open-heart surgeries for curing the pain of ischemic heart muscles was causing a crunch. Standing room audiences spilled surgeons from all over the world into crowded doorways where they hoped to glimpse speakers telling of the latest clinical trials and bypass achievements.
Could it be that a future conference of the American Heart Association will be jammed with overcrowded conference rooms on genetic therapy for relieving the pain of ischemic heart muscles?
The passing of the 20th century leads one to reflect on another watershed moment in the annals of surgery in the U.S. If in the next decade, we could replace bypass surgery by applying genetic therapy through a catheter to grow new vessels in the heart, it would be much like the elimination of routine thyroidectomies in the 1920s when some surgeons were removing as many as 28 thyroids per day.
One in three women in the Midwest suffered from goiters because Mid-western food in the early 1900s didn’t contain enough iodine. Yet after iodized salt added to the diet was shown to prevent the unsightly, grossly enlarged thyroid glands, the surgical procedure became almost obsolete.
So a forecaster of the next century could well predict that we will also see bypass surgery relegated to the long list of now nearly obsolete procedures. Medical students in 1965 were told that “one half of everything you learn today will be obsolete in five years.” That was 35 years ago. Today, perhaps we should be telling them their learning may be obsolete in less than three years. Computers can be obsolete in less than that.
Future conventions of the American Heart Association may be jammed with cardiologists wishing to get a glimpse of the Bill Gates of the gene revolution–Dr. Craig Venter or cardiologists like Dr. Jeffrey Isner–who are threading catheters and growing new vessels in hearts instead of borrowing veins from legs and mammary muscles.
Because there aren’t enough human hearts to transplant all who suffer, we optimistically watch this emergence of genetic therapy.
Injecting the genes into oxygen-deprived leg muscles has worked for several years. Painful claudication of legs is one thing, but it is not as dramatic and life-threatening as angina.
To learn about the pain of angina, physiology students at Indiana University School of Medicine were asked to roll up their sleeves, raise their right arms above their heads for a few minutes, then wrap a tight tourniquet around the upper arms to restrict blood flow from returning to the lower arm. Next, the students plunged their ischemic (blood starved) lower arms into a bucket of ice cold water. The pain was excruciating. As students grimaced and pulled their arms from the water, they were urged never to forget the pain of a patient who suffered from a heart muscle that couldn’t get enough oxygen from its clogged circulation. That is angina!
When severe, the pain of angina is frightening. The Rev. Wilson suffered such pain–a chest pain that followed almost every exertion. He was nearly bedfast.
When we first interviewed Charles Wilson in January, it had been nearly nine months since his gene therapy procedure had occurred on the 22nd of April. He was no longer in pain. In fact, he was walking the malls and riding bicycles for exercise.
With a remarkably upbeat, optimistic outlook, he was making history as one of the first to undergo the experimental procedure at the Coronary Gene Therapy Program led by Dr. Jeffrey M. Isner. His success story must be an inspiration to all who follow it.
Rev. Wilson was eager to share his story with our readers. “I was in the first investigational stage. And they did have to open my chest to give me the shots of the VEGF. I understand now, that they are not doing that, that they are now delivering the VEGF by means of a catheter, and injecting the needle from within the heart. But for me, they made an incision to the left of the sternum and spread the ribs and injected the VEGF in that manner.”
CS: Could you explain to our readers just what VEGF is?
CW: Let me ask my nurses here. I have two daughters who are nurses and my wife is a nurse. (pause)
“VEGF is Vascular Endothelial Growth Factor.” But it is synthetically produced. I was very careful to inquire about this because of my beliefs. I couldn’t have used cells that had been taken from a fetus.
When I inquired about this, they assured me that these were “naked DNA’s.” I asked, “What does that mean?” They said, “That is your assurance that it is synthetic.” DNA taken from the body can never have all the protein removed from it, and to say that it is naked DNA is saying that there is no protein there and it had to be produced in a laboratory.
CS: They can reproduce the gene that you need from the formula that they have been able to sequence out. And with the synthetic product, there is no protein to cause a rejection problem?
CW: Right, they couldn’t remove the protein from the human DNA. If they gave it to me, we would have all the rejection factors that transplant patients have to live with–unless I am behind in my medicine here. I am not a doctor, but I read a lot of this stuff.
CS: Have you had any subsequent treatments ?
CW: Oh, no, it was one treatment. They injected the VEGF in four different places in my heart, and within a month I was beginning to feel better and started exercising, and have continued to improve since that point. Prior to the treatment, I was having 20 to 25 bouts of angina a day.
Everything I did would bring chest pain and shortness of breath. I even had to get a shower chair so I could sit to take my shower. I would have so much difficulty just taking the shower that when I finished I would have to lie down and rest until I could go again. From something as mild as taking a shower and going up steps to anything that required more exertion than that brought pain.
My doctors here in Charlotte basically said, you just need to sit still and wait on technology to catch up with you. I saw a little article one day about the coronary gene therapy, and I went online and began to research it. I called St. Elizabeth’s Hospital and asked if they would consider me, and they asked that I send my medical records, which my cardiologist did. I was thankful that my cardiologist here in the city was so cooperative. When I went up, they said, “Yes you are a candidate,” and two weeks after that, they did this surgery and gave me the injection.
Being in the initial stage guaranteed me the VEGF. I was technically considered the first person in stage II of the initial stage. They had made some minor changes in the VEGF at that point.
CS: Were they going to do double blind studies?
CW: At that point, they weren’t even considering the double blind, but they are doing it now. I think they have found a very compassionate way to give the double blind. What they do is deliver the VEGF by catheter. They give you two caths–one now and one three months from now–and on one of those two you are going to get the VEGF. In other words, people who get the placebo the first shot get the VEGF the second shot.
CS: Oh that is good.
CW: So the maximum that anyone would be put off once they are accepted into the program, would be the three-month time frame. But I was assured that I would have the VEGF. I think they did 5 or 6 patients after me, before the FDA let them start the double blind study.
This treatment actually developed and grew out of Dr. Jeffery Isner’s studies, where he was using this VEGF to grow bypasses in the legs. They began to look for other places that it would work, and they of course saw it would work in the heart.
CS: Tell us about your life now. How much exercise are you able to do?
CW: I go to the mall at least five times a week, and I am walking about 2.5 miles each time I go. Also, in the evening I ride a stationary bike for three minutes and I try to do that five times a week. I don’t always do both exercises each day, but I try to do five of each. So I end up some days walking but not riding the bike, but usually three or four days I will have both exercises.
CS: Wonderful! Did anyone ever suggest swimming to you, or did that not appeal to you?
CW: I never have been a good swimmer. I used to swim laps some when I was in college, but I had difficulty breathing.
CS: After your gene therapy, are you now able to preach?
CW: I have not been able to preach for a couple of years. I have told many friends recently that I would be willing to fill the pulpit for them. I did fill the pulpit a few months ago, just to test myself to see if I was ready to go back to those rigors. I did not notice any chest pain as I was preaching, but was aware of some chest pain after I stopped. So I backed away and said, “Okay, I am moving too fast. I shouldn’t be having chest pain when I am preaching or immediately following it.”
CS: Is there any likelihood that you would benefit from additional VEGF therapy?
CW: Well, I really don’t know at this point. I guess that is one of the disadvantages of being in a study of this nature–you don’t know all the long range results, positive or negative. I am still improving at this point. I have asked them if I will improve to the point that I will be able to go back to work full time. They said, “We can’t answer that for you. We just don’t know yet.” I am able to do the basic activities of life now without any pain. I guess the biggest problem I have right now is fatigue, but that is so much better than what it was last April that I hate to even mention it.
CS: So you haven’t had to take any immunosuppressant drugs to reduce the chances of any kind of rejection at all?
CW: No, Ma’am.
CS: Have you had to take any kind of medicine after your therapy?
CW: I am still on my heart medications, but we are reducing some of those.
CS: You mentioned a BBC taping you had done. When will this be shown in the U.S.?
CW: It will air in about April or May in England; then next summer it will be shown on ABC. It will also air on the Learning Channel here. They are doing a series. When they interviewed me, the program was titled, “The Human Body and Modern Medicine: But they said that that is just a working title. They do not know what name will be on this when it is finally finished. But they were covering a lot of different subjects. Basically, they had been to Boston to look into the gene therapy program at St. Elizabeth’s, and they saw a NOGA map that had been done on me. It shows the results so dramatically that they said, “Let’s talk to him.”
CS: What is a NOGA map?
CW: It’s a map that shows the amount of blood flow to the heart, where the ischemia is in the heart, and how the heart is moving because of the ischemia. At St. Elizabeth’s, they do a NOGA map before they inject you with the VEGF.
Then they use that map to determine where to make the injections. They can see healthy tissue. They can see the ischemic tissue and scar tissue, and of course, they put the injections into the ischemic tissue. On myself, I am going to estimate that 70 percent of my heart was ischemic. They showed me the pictures and said the brighter the colors, the worse the ischemia. A good portion of that 70 percent had real bright colors in it–almost orange. That was the before picture. In the after picture, maybe 15 or 20 percent of my heart at the very bottom had the bright colors.
When they gave me my copy, they said, “This is for you. You may tell people about it. You may show it to people, but you cannot give it to anyone until you have our permission, because you are part of the investigational study.”
I have shown the NOGA maps to other patients. Because stories have shown up in the New York Times and the Charlotte Observer and other papers, people will call and talk to me. I am glad to tell them what has happened. In fact, I see sharing my experience as one way of expressing my gratitude to the Lord for being so gracious to me. When I am able or geographically close enough to someone, I show them the pictures. In fact, I had them with me in Boston about three months ago. There was a man who was staying in the same hotel. He called with questions. So I talked to him, answered his questions, then showed him the NOGA pictures. After that, he decided to go ahead into the gene therapy program.
CS: Do you now have the before and after NOGA pictures of the perfusion of your heart and how it acts?
CW: Yes, Ma’am.
CS: It’s like an ultrasound printout?
CW: In a sense it would be like an ultrasound. When you do those radioactive treadmill tests, they scan off a picture, and this picture is similar to those. Actually, the one they gave me used colors like they do on the weather map on the news on TV. The greens were normal, the yellow area indicated the bad ischemic area–the brighter the yellow, the worse the ischemia–and the red was scar tissue. It is amazing how much of the heart changed from yellow to green healthy tissue.
CS: Is St. Elizabeth’s the only place this is being done, to your knowledge?
CW: There were other places that had other ways of administering the VEGF that did not work. Actually, there was one place that would administer the VEGF by putting it through an IV. You went in every day for a week and they would put the VEGF into the IV, but the body just flushed it out. Then there was another place that would administer the VEGF by doing a cath and just spraying it into the heart. But here again, that washed out. And so St. Elizabeth’s was the first and only place when I had my treatment that was actually injecting it into the muscle. Since then, I think there are two other places that have begun to inject it
CS: Now, do I understand that no longer will they need to open up the chest to inject it? They can do it with a catheter?
CW: Oh, they can now. They could not when I had it. But now it is administered through a catheter. There is a needle at the end of the catheter, and they thread it up and just shoot it inside the heart.
CS: And they thread it through your leg?
CS: Well, that is a fairly noninvasive procedure.
CW: Oh, yes.
CS: Could you describe the procedures you had before you read about the coronary gene therapy program?
CW: I have actually had two separate bypass surgeries where my chest was opened and veins were taken from my legs and from my chest wall and bypasses put in. I have had about seven balloon angioplasties and one laser angioplasty.
CS: Have you always had high cholesterol?
CW: Yes Ma’am. In fact, three of my children have high cholesterol, and we are treating them and have been treating them for cholesterol problems since they were three and four years old.
CS: Is that right?
CW: I was the oldest of 4 boys and the first grandchild. My grandfather apparently died with a heart attack caused by high cholesterol. My mother was the oldest of 10 children. Almost all 10 of those children showed up with high cholesterol and coronary artery disease. I was the first grandchild, and now most of the grandchildren are showing up with coronary artery disease, and as I said, three of my children are being treated now. To give an example of how high their cholesterol levels are running, these kids–at three, four, five years of age–had never had sweets. They never had anything but what would be considered a heart-healthy diet. And their cholesterol was running anywhere from 350 to 380.
CS: Did anyone ever put them on niacin?
CW: Yes, and they had reactions to niacin, and their liver enzymes went real high. I am on niacin now, in addition to Lipitor and Questran and Tricor. All four of those are to lower cholesterol and triglyceride levels. Of course, they now have me on folic acid.
CS: To lower your homocysteine level?
CW: Yes, Ma’am.
CS: Have you ever had high homocysteine levels?
CW: Apparently, I always have. But we didn’t know to check it until the last couple of years.
CS: Once it was checked, do you know at what level it was?
CW: No. They told me, but it didn’t register.
CS: I think that in our labs the normal range is between 6 and 12.
CW: I could get this lab report for you.
CS: We would really like to have it, because I think that homocysteine may be as important as cholesterol, and it is a lot easier to lower homocysteine levels with folic acid than it is to lower cholesterol. In your case, taking niacin caused your liver enzyme values to go up?
CW: No. My kids’ levels went up, but mime didn’t. I am doing all right with the niacin. They are giving me a long acting form of niacin
CS: Have you read of any criticism of gene therapy?
CW: Any change looks to be liberal quite often. I expect there are those in the medical world who think that all the genetic studies are very liberal. And, in fact, I have read some of the articles that point out all the things that are supposed to be wrong with genetic medicine. I am not sure I agree with them. I remember seeing some of the articles where they were using the gene therapy, but they were not injecting it into the muscle. It was where they were squirting it into the heart.
CS: Scientists are also hoping to use gene therapy to out-fox cancer cells.
CW: One of the things that they did when they screened me to see if I was a candidate for the coronary therapy was screen me for cancer, because if I had had cancer, this therapy would have made the cancer grow. If this vascular endothelial growth factor (VEGF) hits the cancer, my understanding is that it causes it to explode like a nuclear blast. In fact, the doctors at St. Elizabeth’s explained this to me.
When I asked them how many people they had screened for the program, they told me that they had screened between one and two thousand actual applications, but they asked only about 140 to 160 people to actually come to the hospital and go through their screening and testing process. I was the 30th person to be accepted. When I asked why the others were turned down, I found out that in some cases another procedure could have been used–in other words the applicant might be a candidate for another bypass surgery or that a laser or balloon angioplasty would work for him or her. But in several cases, they said that they found people who could have used the gene therapy but were unable to receive it because they had cancer. The doctors said that it was the hardest thing to tell these folks, “We would like to give you the gene therapy, but you have cancer.”
CS: They didn’t know they had cancer?
CW: They didn’t know it. Then these people were told to go home, “take care of the cancer, then come back and see us, and we will put you in the program.” I found the doctors at St. Elizabeth’s to be most compassionate, almost as if they were men from a different age of medicine. They had time to stop and talk to their patients. They had time to explain what they were doing, or they took the time. Maybe I should put it that way. And you know the average doctor doesn’t do that anymore.
Harvard and Tufts medical schools are both right there within a stone’s throw of one another. I found Boston to be an interesting place.
I was very thankful that my cardiologist here in the city was up to date on things enough that when I called him and said, “Would you send my records?” he said, “Yes, sir.” Of course he has become very aggressive in dealing with cholesterol problems now. His group of doctors have started a preventive cardiology department. You might want to talk with him about homocysteine levels.
CS: I shall.
CW: He is Dr. Daniel E. Wise. He is with Mid Carolina Cardiology.
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