Heartfelt gift helps fund amyloidosis care at MUSC

Darby. It’s a familiar Lowcountry name. And tucked away in an unassuming part of Mount Pleasant is an office building that bears the name.

A Darby and a Boykin named Sassy promptly greet you as you enter. Soon, you’ll meet other members of the family — just more subtly.

A Mount Pleasant native, Gordon Darby sits behind his desk in a manly yet understated office. He’s surrounded by photos of beloved family members — whose names it gives him joy to speak — their images a constant reminder of the important roles they play in his life. Wildlife art paints the wall, save for the spot with the big-screen TV that has a business network silently running in the background. Even from the solitude of the woods, the world of high finance is never terribly out of sight.

The epitome of a true Southern gentleman, he rises from his chair, as spryly as he would have 40 years ago. If his joints bother him, they do not betray his hospitality. Standing displays the physique of a college athlete, a testament to a life spent on the gridiron, exercising and eating right.

When he set out on his own in 1968, he didn’t have much more than a few dollars in his pocket, he said. Today, it appears, he has quite a few more than that. Still, the irony does not escape him that despite all his healthy efforts and the good Lord blessing him abundantly with family, looks and success, he is dealing with a rare and life-threatening condition that is completely out of his control.

Amyloidosis.

But Darby, never one to sit back and wait, plays both offense and defense these days. He’s educated himself on the disease. He’s sought the finest care. And he’s invested half a million of those hard-earned dollars to try to help tackle a disease for which there is no cure, having recently funded the beginnings of the MUSC Amyloidosis Center of Excellence.

Heart Failure

A word that many are familiar with, amyloid is often associated with the plaque that causes Alzheimer’s. Actually, it’s a broad term that covers any protein that misfolds and then deposits and builds up someplace in the body, like organs, interfering with the way the organ’s supposed to work.

Like the heart, for instance, where it affects Darby.

Amyloid deposits in the heart cause cardiac amyloidosis, and, as deposits increase, the heart becomes stiffer.

The job of the heart is to pump out (eject) oxygen-rich blood to the entire body. In a healthy heart, the heart muscle relaxes after each contraction and allows the heart to refill with blood. If the heart loses its ability to relax normally between beats because the muscle has become stiff, it can't fill with enough blood. So when the heart squeezes normally but is too stiff to relax and refill properly, that condition is known as heart failure with “preserved ejection fraction” (HFpEF). Studies have shown that up to 15% of patients with HFpEF, like Darby, are found to have various kinds of amyloids in their hearts.

Swelling, fatigue, dizziness and shortness of breath are common when amyloidosis affects the heart, but they are also common to other ailments, so doctors often don’t make the amyloid connection early enough.

Beginning around 2015, Darby noticed subtle changes — like his feet would swell.

“I found I was uncomfortable in my shoes and boots. I do a lot of hunting, and that wouldn’t do. It was the first sign I experienced; it was sort of an ebb and flow.”

He also found himself at the end of the day uncharacteristically fatigued. And he was getting up four or five times during the night, which also concerned him. He saw his urologist.

 

But it wasn’t until his annual physical with William Wingfield, M.D., that anyone put two and two together. Wingfield discussed his findings with Blount Ellison, M.D., Darby’s cardiologist, and Ellison made the diagnosis based on Darby’s history and echocardiogram.

That, Darby said, really got the ball rolling.

He called his brother, physician Charles Darby, to seek his counsel. A legend in the medical community, he founded the MUSC’s Children’s Hospital in 1987, and the Charles P. Darby Children's Research Institute was named in his honor in 2005. He suggested that his brother make a trip to Boston Medical, one of the top two centers at the time, for evaluation. There Gordon Darby met Flora Sam, M.D., and the two developed a friendship.

Two years later, nationally renowned amyloidosis expert Daniel Judge, M.D., was recruited and joined the cardiology team at MUSC Heath. His goal was to create a national center dedicated to the study and treatment of amyloidosis. While the two remain friends, Darby told his Boston doctor that he would receive his care at MUSC.

It was a very good decision, he said.

In good hands

In addition to being one of the country’s leading authorities on amyloid disease, Judge has combined expertise in heart failure, cardiovascular disease and genetics. As far back as 2004, when he was honing that expertise at The John Hopkins Hospital, he developed a database of patients with amyloidosis, participated in clinical research and wrote papers on his findings.

But with no good therapies available to halt the progression of the disease or offer a cure, he was frustrated with how everyone with cardiac amyloid was given the same terrible prognosis.

“When I was training in the late 1990s, when we were able to find amyloid, it was through a biopsy of the heart. The only thing we could tell people was to get their affairs in order — there is no treatment.”

The average lifespan in the late 1990s for someone diagnosed with heart failure due to amyloidosis was approximately six months. Delivering that news was difficult. “It was terribly depressing. It was an awful diagnosis to give a person. Thankfully, this prognosis has changed substantially in the past 20 years.”

Today, he said doctors can offer these patients hope.

Judge explained the two main forms of amyloidosis that affect the heart.

The first is amyloid light chain (AL) amyloidosis. Associated with multiple myeloma, a cancer that forms in a type of white blood cell called a plasma cell, it circulates through the blood and can deposit in the heart, kidneys, nerves and other sites.

“That’s the worst form, and it has the worst prognosis,” Judge added. “But the new treatments that our hem-onc specialists [hematology oncology] now have are way better than they were several years ago. Here at MUSC, we’re doing bone marrow transplants for those patients. If the heart is affected, it’s more challenging. We do everything we can to optimize their heart care.”

“So, the first fork in the road is — is this the cancer kind? If it’s not present, the second form we look for is called transthyretin amyloid.”

Transthyretin is a protein that transports thyroid hormone and retinol (vitamin A) within the blood, forming the hybrid name — trans-thy-retin or TTR.

He explained that TTR amyloidosis breaks down into two main subtypes. The first is genetic, and the other seems to appear out of nowhere, called wild type.

In the first, a genetic tendency can be passed from one generation to the next. Symptoms can begin to develop anywhere between the ages of 20 and 70.

Wild-type TTR amyloidosis does not involve abnormal DNA, so it is not passed on to family members, and it usually affects men in their 70s and 80s.

However, experts have identified an interesting phenomenon. Bilateral carpal tunnel syndrome can actually be a symptom that occurs much earlier, serving as something of an early warning system. When the dots are connected, amyloidosis can be found in individuals as young as their early 50s. Similarly, recent research suggests that lumbar spinal stenosis, rupture of the biceps tendon and bilateral joint replacements — like hip and knee — can also precede cardiac involvement by many years.

Darby feels like the poster child.

In 2003, he had his Boykin Molly tucked in his arm, climbing up to a deer stand. About halfway up, he heard a pop. He’d torn his bicep tendon.

Today he understands that was a telltale sign of amyloid.

“I’ve learned a lot from Dan Judge. For instance, in 111 people with amyloid, 33% had bicep ruptures prior to diagnosis. Normally, it’s only 1 in 1,000. The other connection that’s extremely important is joint replacements. I’ve had a lot of surgeries – all seemingly related to athletics. Both shoulders replaced. Knees. Hands. I mention that to my doctors, talking about amyloid, and they’ve never heard of it — stare at me like a deer in headlights.”

That bothers him.

“I told Dan that we need to start talking about this when they’re in med school. Get the word out to the orthopedic community that when patients come in with these things, they need to be checked for amyloid. Putting it into med-school curriculums and starting awareness campaign for orthopods is near and dear to my heart.” 

Judge agrees. And he believes amyloidosis is much more prevalent than once thought.

“There are a lot of amyloid cases out there; it’s just not being recognized. We have a lot of work to do around this.”

 

Darby isn’t leaving that responsibility to someone else. His recent $500,000 commitment will help to coordinate amyloid care among specialists at MUSC Health and ensure better diagnosis, management and research about this condition and facilitate outreach efforts nationally and internationally.

Judge said that there are three major components to a successful amyloidosis center of excellence. First, making sure patients have not just proper diagnostic strategies but better therapeutic strategies — things that are on the way. Second, research to understand demographics and why it happens.

But it was the third part he couldn’t emphasize enough.

“That is the educational aspect of it, both to providers and to communities — the Charleston community, the Southeast, the U.S. — building awareness. If you have heart failure with preserved EF or a stiff heart, you should be asking your doctor about amyloid. If you have carpal tunnel, you should be asking your doctor about amyloid, because there are good treatments.”

Luckily, Judge is in a good position to get the word out. He is one of about 10 recognized experts in the U.S. on the subject who are seen regularly on the dais at national and international meetings in the company of distinguished programs such as the Mayo Clinic, Boston University and Harvard’s Brigham and Women’s.

“When I’m giving a lecture on this, I’ll ask the audience how many of them have seen amyloid or made a diagnosis of it in the last six months. If not everyone raises their hands, I say to them, ‘You’ve probably missed cases.’ There is a really high incidence of it, and it’s poorly recognized.”

Pieces of a puzzle

Darby is cautiously optimistic about his own future but thinks more about those who can be helped in the years to come. He doesn’t want his loved ones to hear the word amyloidosis — let alone worry that there is no hope.

“This damned disease is something… it comes on so gradually,” he said. “The symptoms — there are a lot of people who have them that don’t know what’s going on. They’re not real blatant problems — not like high blood pressure or cholesterol where you can get on a med. I never had shortness of breath. Swelling and fluid was it. I’m in great shape for an 81-year-old guy.”

That is a huge point of pride for him. He was exercising, he boasted, long before it was popular. He was maybe 11 when the workout bug bit him, and he hasn’t stopped since. That’s partially why it was such a big blow to his ego when he found out he had this disease.

“I was 35 or 40 years ahead of my time with regard to preventive health and exercise. I’m from the generation that smoked, drank and didn’t give a damn what they ate. They didn’t exercise and thought you were crazy if you exercised. Both my brother and I came up in that era. I believe it was some kind of intervention — divine intervention. I looked at people who exercised and stayed in shape and wanted to be like them.”

That’s never wavered. He gets up at 4:30 every morning. He goes into the office and conducts business every day. He hasn’t had a drink since 1987 and hasn’t bought meat from a store in 40 years. He never smoked, and whether he was playing basketball and football in high school and college or he’s hunting or gardening now, he’s always preferred being active.

His only vice, he said, is he can’t turn down pecan pie with a big ol’ dollop of whipped cream — and his wife, Anne, well, she makes the best there is from their own pecan trees.

“I haven’t told my doctors that yet. I don’t know that it matters… at 81, you’re getting to the front of the checkout line anyway,” he said with a laugh.

He’s currently in a trial. He started the trial in September of 2018 and in November, found out that he had been on the drug — not the placebo — from the beginning. For that, he’s incredibly grateful.

“I have to say, maybe I’m better. It’s a fatal disease. Of course, we’re all going to meet our maker at some point. But for me, the important thing is the quality of life. I told Dan when they put me on Eliquis about two months ago — because there were signs of clotting in my heart — that I don’t fear death. But I do fear having a stroke.”

A magic bullet?

Every patient hopes for a cure. So do their doctors. Judge’s enthusiasm is fueled by the promise of new medications that are emerging for the different forms of amyloid. A year ago, there were no Federal Drug Administration-approved medications available for patients in the United States with amyloidosis. Now, one’s in trials, AG10, and another recently approved by the FDA, Tafamidis, has great potential to help, he said.

But there’s a hitch. Tafamidis costs $225,000 a year. In some cases, insurance will pay, but with the bulk of patients on Medicare, there are challenges with copays and donut holes, the coverage gap that limits how much a drug plan will cover, Judge said.

Judge is hoping competition will eventually drive prices down.

Darby is taking its competitor, AG10, manufactured by Eidos Therapeutics, which recently began phase 3 trials. Judge is the lead principal investigator, and MUSC was the first site in the world to enroll patients in this trial, which will target 500 patients. Judge established some of the initial data in the phase 2 trial, which showed in a cohort of 50 people that it was safe and effective.

Two other drugs for inherited TTR amyloid with neuropathy were approved in the past year. Both have price tags of about $400,000 a year.

So at the moment, hope comes at a cost.

It’s one of the reasons Darby is so proud to have made the inaugural gift.

“There are no magic bullets out there. There is no cure. This center is really needed. If the money I’m giving doesn’t help me, the people who follow me will benefit. That’s what life is all about – isn’t it?”

It’s a comfort to him, he said, to know that MUSC Health has an expert team of heart doctors in his backyard.

“The team is top-notch. There is no doubt about that. There is no other amyloid center in the Southeast; my only option was to go to Boston or Rochester, Minnesota. There’s a lot of folks who have this disease and don’t know it… until it’s too late. This could be a time bomb here in the Lowcountry with all the heart disease in South Carolina.”

Judge still sees some of his patients from Maryland and Virginia, who now come to MUSC Health to see him.

“I’m honored that several of my patients have chosen to follow me here. I have many long-standing relationships that I established with my patients with this condition, many of whom are doing very well years later.”

Now, people come from all over, and it’s important to him to build relationships with them.

That warmth hasn’t escaped Darby. “I have a lot of confidence in Dan. Dan is a man who sincerely cares about his patients. He’s very caring — Tom di Salvo and Jeff Winterfield, too. Good men. God knows they’ve been here for me.”

These comments humble Judge, who immediately turns the conversation to the other amazing heart failure experts on the team — eight in all.

Today, there is more to be hopeful about than ever before for people with amyloidosis. But with numbers on the rise, MUSC is eager to get the comprehensive center off the ground — and raising $5 million to launch it will allow specialists to advance their research, develop better treatments, get the word out far and wide — and, hopefully, one day, find the cure.

Judge feels MUSC is in a unique position to accomplish this.

“I’m biased, but I think we’re clearly by far the best when it comes to novel drugs or therapies for this condition. We just recently did a heart transplant for somebody who has this condition, and we’re the only heart transplant center in the state. What we can offer is far beyond what anyone else in the state can offer or even in some cases, the region.”

Darby agrees. “I don’t think this disease is rare, just rarely diagnosed. With a dedicated center, think of all the lives that might be saved.”