Gene Therapy: Who Makes the Decision?

by Derek L. Markley

It has been more than eight years since St. Jude Children’s Research Hospital, University College London, and the Royal Free Hospital began a clinical trial using gene therapy to treat people with hemophilia B.

Derek and his son, Bubba

That same year, our family welcomed a new baby, Bubba, who has severe hemophilia B. We had recently located to central Illinois from east Tennessee when I accepted a position with Eastern Illinois University. Bringing a new child into the world is a wonderful and stressful time for any family. As parents who had no experience with bleeding disorders, my wife and I were wholly unprepared for a hemophilia diagnosis.

Six months after Bubba was born, I was headed to lunch with a friend after meetings in the state capitol building. I can still tell you exactly where I was standing when my friend handed me her phone and asked if I’d seen the New York Times article about gene therapy and hemophilia B.

Fast forward a few years, and we again relocated, this time to Tupelo, Mississippi. We were very fortunate to become patients at St. Jude. Little did we know that Bubba’s physician would be one of the primary investigators in the gene therapy clinical trial. All of a sudden, the world of gene therapy was thrust directly in front of us.

We are now in a position, like many other hemophilia families, where the reality of a cure for hemophilia seems within reach. Presently, three phase III trials are beginning to test the efficacy of gene therapy in treating hemophilia B. Clinical research does not move quickly, but advancements in gene therapy over the past eight years have been amazing. The FDA has released new guidelines regarding gene therapy development, and funding for these ventures is in overdrive.

If gene therapy treatment becomes a reality, I’m forced to ask these questions: Is this a decision we can make for our son? Do the parents get to decide? How do we talk to our son about the risks and rewards of such a treatment? Bubba is only eight now, but it seems wise to begin thinking about how we’d handle this situation. Of course, the question is moot if insurers, treatment providers, and pharmaceutical companies can’t agree on a feasible reimbursement strategy. There are a lot of variables at play, yet the advancement of gene therapy treatment demands that Bubba’s mother and I begin thinking about how we will make decisions if a gene therapy treatment becomes available for our son.

It’s amazing that, of all the health conditions in our world, science and medicine have combined to put a treatment for our son’s type of hemophilia at the forefront of gene therapy.

Bubba is a very active kid. My wife describes him as “all boy.” His condition has done nothing to slow him down. Bumps, bruises, cuts, or scrapes, he weathers them all and refuses to be limited by his uncooperative blood.

We’re reaching a time where Bubba’s questions about hemophilia have become more mature, requiring us to be more introspective when talking with him. The greatest question we face is how do we determine his role in a decision about treatment if gene therapy becomes a reality? It is his life, and, like all parents, we hope that he’ll be around for a long time after we’re gone.

Bubba views infusions as an inconvenience. We know he secretly wants to play quarterback or wide receiver. He knows that hemophilia makes him different from his friends. Different isn’t always easy for kids to understand or accept.

The problem is that his mother and I have more complex questions, not that Bubba’s questions are unimportant. What if our government decides to once again unfairly punish people with pre-existing conditions? What if Bubba is in a serious accident? What if he develops a target joint? There are a million tough questions. What makes the situation even harder is that these questions are about things over which we have little or no control. There are far more questions than answers.

The best answer we have right now is that we’re thankful for the treatment presently available for our son and the prospect of what some are beginning to call a cure. There are too many parents with children afflicted by conditions that have no available, effective treatments. When we picked Bubba up after his first bleeding disorder camp last summer, he told us that some of the kids said he was lucky because he only infused once a week. I think those interactions gave him his first insight into the fact that living with hemophilia is not the same for everyone.

Science can do amazing things. As a species, we’re quite ingenious at times. I have no doubt that hemophilia will cease to exist one day, but I have no idea when that day will come. As parents, we can only put our son’s best interests first, stay informed about medical advances, and trust that our team at St. Jude will continue to help us make the best decisions based on the options available.

Bubba won’t want to hear it, but his mom isn’t going to let him play football anyway.


Derek lives in Saltillo, Mississippi, with his wife Ashley and their children Abbey and Bubba. He is the executive director of two University of Mississippi regional campuses and an assistant professor in the School of Education. Ashley is a fifth-grade math teacher in the Tupelo Public School District. Derek is the author of The Bubba Factor, available on Amazon in Kindle format and in paperback.

The Day of Living Dangerously: Haiti

The rocks in the water don’t know how the rocks in the sun feel.—Haitian proverb

Poverty in Haiti

Haiti is the poorest country in the Western hemisphere, and even during good times is never easy to visit or work in. A government that seems perpetually corrupt, combined with natural disasters (most notably the earthquake of 2010), difficult topography, lack of infrastructure, and massive inflows of foreign aid have left this island nation dependent, poor and frustrated.

The frustration reached a peak last week, when riots erupted in the capital, Port-au-Prince, and the second largest city, Cap Haitien—right where I was. I flew from Boston on Sunday, February 10, after at least 7 months of planning, and 16 years in the making. At last, I was going to start a hemophilia program in the country. Yes, 16 years in the making. That’s a story for another blog.

I landed on Sunday and was home Monday night. Only 24 hours in Haiti. Almost all our plans foiled. But it was not a total loss. I was able to meet two of the 11 boys I know with hemophilia. And that made the whole adventure worthwhile.

Vendor shack

I met up in Miami on layover with Barbara Campbell, executive director of the Dalton Foundation, which does a lot of great health care work in Haiti. Her group is connected with the Cap Haitien Health Network (CHHN), a nonprofit based in Orlando, which has guided me for the past 11 years in trying to establish hemophilia care. Barbara is competent and energetic, and obviously loves Haiti.

This is the irony of Haiti: as bad as it gets, as frustrating as it can be, there is something compelling about the country and its people, especially to Americans and American missionary groups. Perhaps because it is only a 90-minute flight from our shore: we feel a kinship with this sad piece of earth. Perhaps it’s because we know there must be a solution; I mean, it’s a tiny country—how hard can it be to fix? It’s right in our backyard. Let’s bring in the help, the food, the seeds, the money, the medicine, the manpower—let’s fix this place up! It hasn’t quite worked out. For all we have invested in Haiti, it festers in the heat. And still we want to make it the beautiful country it should be.

Two hours later, Barbara and I landed in Cap Haitien, and were met by our driver, “Charles,” who also happens to be a lawyer and CPA. The day was sunny and surprisingly dry, and I looked forward to an afternoon with two brothers with hemophilia. But Charles told us we were not going to the hotel first, as planned; it would be too dangerous to drive in and out of that area twice. There were roadblocks and bonfires in the streets, and protests. Better to go see the boys now, and make only one trip into the gated Hotel de Roi Christophe. We piled all our luggage (mostly gifts) into the small van and took off. We got lost a few times, but it was a quick 30 minute ride to the boys’ home. The roads were worn and torn, and traffic was light. We got lost a few times but finally pulled up to a quaint, deep turquoise-colored single level house on a packed dirt road.

See photo gallery of trip here.

Steven Saintil

There to greet us is June Levinsohn, an American from Vermont, who has worked in Haiti for 30 years and speaks fluent Creole. Spry and direct, June is one of the most dedicated people I’ve ever met, and her dedication and knowledge gives her the right to be honest and blunt when speaking about Haiti. And it was June who helped put us in touch with the two brothers. June saw a photo of Steven Saintil in the Coastal Haiti Mission newsletter back in early June. No one seemed to know what was wrong with the child with the swollen knees in the photo, but June asked Dr. Ted Kaplan of the CHHN, who then referred the child’s case to me. Looking at his knees, we all suspected hemophilia. In an extraordinary feat—keeping in mind none of us had even met—we had Steven’s blood drawn and flown into Miami, where a pathologist I know picked it up and diagnosed Steven with severe hemophilia A! And Project SHARE began sending factor to him last September, via his local doctor.

Steven and his brother Louvens, who has hemophilia too

There to greet us is June Levinsohn, an American from Vermont, who has worked in Haiti for 30 years and speaks fluent Creole. Spry and direct, June is one of the most dedicated people I’ve ever met, and her dedication and knowledge gives her the right to be honest and blunt when speaking about Haiti. And it was June who helped put us in touch with the two brothers. June saw a photo of Steven Saintil in the Coastal Haiti Mission newsletter back in early June. No one seemed to know what was wrong with the child with the swollen knees in the photo, but June asked Dr. Ted Kaplan of the CHHN, who then referred the child’s case to me. Looking at his knees, we all suspected hemophilia. In an extraordinary feat—keeping in mind none of us had even met—we had Steven’s blood drawn and flown into Miami, where a pathologist I know picked it up and diagnosed Steven with severe hemophilia A! And Project SHARE began sending factor to him last September, via his local doctor.

And here we were now, with Steven! Although 11, Steven is small, but I am happy to say his knees look a lot better than before. With the factor donations, he was able to return to school, which is just down the road. It’s a Christian school, and Pastor Cody, who looks out for Steven and his half-brother Louvens, was with us that day.

Steven and Louvens knew who I was, and I interviewed them a bit. The father of each boy is gone, disappeared, not wanting to deal with a sick son. The mother is dead; she died from a parasitic infection six years ago. “The doctors pulled a worm out from her,” June shared,  “that was working its way out of her body through her arm. Her infection was too far gone by the time she sought help.” The boys are now orphans technically, and live with their aunt. The aunt has a small son as well. The house was neat, with furniture and a toilet—which surprised June—but it was not functioning. Concrete walls and floor, lots of dust, but lots of vegetation to give it a more cultivated look.

Thanks to uniQure employees for the toys!

The boys look clean, well fed, and happy. And happier still when I opened the duffel bag filled with toys donated from uniQure! I had asked the boys if they had any toys, and they shook their heads. Pastor Cody said, “They find things to play with—a tire, a stick.” Now they had pads of paper, markers, Black Panther coloring book (kudos to whoever donated that! Huge hit), small soccer ball, more coloring books, backpacks, soap, toothbrushes, cold packs, crayons, Matchbox cars (small war waged over who would keep those), and more. Now the boys smiled widely and really warmed up! I had also printed out a photo of Steven using a walker; the photo fascinated the boys. Now Steven was walking better, but damage had been done. His hip now thrusts out to overcompensate, which could lead to problems down the road. We will need a PT in soon to help teach the local PTs how to correct this.

Laurie Kelley with Steven and Louvens

Due to the escalating violence, we had to cut our visit short. With high fives, we said goodbye, and piled back into the van. June was staying with friends, and Barbara and I headed back to the hotel. As we neared the center of Cap Haitien, a scene as horrifying as the riots appeared. Absolute mountains of trash undulating on the beach. Cap Haitien sits on a bay, where fishermen catch their daily wages in handmade dugouts. They were barely visible in the bay due to the heaps of trash. I’m used to seeing trash on the street in developing countries but this range could have its own name and topography. Colorfully dotted with ubiquitous blue and pink plastic bags, the everything in their way.

Turning a corner towards our hotel, we could see the smoldering ashes of where the bonfires had been that day. A UN Peacekeeper tank rumbled by, startling us as we took a right, and police cars patrolled. The crowds were mostly dispersed—it was suppertime—“But they will come back tonight,” Charles warned. “Do not go out.” He rocketed at high speed, crushing through one faltering barricade and dodging others, to reach the hotel gate, which was locked. “I’ve stayed here many times,” said Barbara, “And they never lock the gate…”

Barricades

At the hotel, Barbara and I checked in; though run down, the hotel was pretty. There were large cracks in the concrete walls and foundation, and desiccated leaves cracked under our feet. We had a delicious dinner and shared our personal stories—hers was fascinating! And then returned to our rooms to check email.

Not long after dinner, Barbara poked her head into my room and said, “We have to leave.” The riots had escalated in Port-au-Prince, and rumor had it that Cap Haitien would explode as well, especially if guns entered the equation. While it might not happen tonight or tomorrow, riots later in the week might mean the airport would shut down. The airport is small, and has almost no security. We had meetings scheduled the next day with the Cap Haitien Health Network to introduce hemophilia, and then a 5 hour road trip to Port-au-Prince, and then the finale—after 16 years of searching, a meeting with what might be our first HTC in Haiti.

Mountains of trash.

None of it was to be on this trip. We booked the next flight out of Cap Haitien, Monday at 1:35 pm, about 24 hours after landing. As surreal and foolish as it all felt—after all, there was nice Caribbean music coming from the bar in the lounge, and birds hawking overhead in the tree—the situation could turn on a dime. Our colleagues in PAP confirmed it; meeting cancelled, and the US Embassy was issuing advisories and warnings not to travel to Haiti, and for Americans to leave.

The next morning, we packed quickly—I had barely unpacked—and Charles came early to take us to the airport. At 8 am, as we turned down the street, we encountered the first demonstrators. A bonfire raged in the middle of the street as a crowd gathered. About 50 feet away, an angry young man in a red t-shirt spied us and hurled a rock at our windshield. Others got ready to throw and we heard the rocks pelting around us. Charles bravely leaned out and shouted in Creole, waving his arm. The man seemed a bit startled and confused. Luckily, we were hidden a bit in the back seat, our windows darkened. Though I badly wanted to take a photo, I knew this could attract the anger of the crowd too.

The man waved us through. We sped to the airport and in 15 minutes were there. We were the first to arrive. Eventually the American Airline agents showed up, and had to hand write our boarding passes. In Haiti, anything goes. From there, our lives went on smoothly. We checked luggage, boarded the plane, connected in Miami, and separated to our homes.

For those in Haiti, they were home, which was descending into a dangerous madness.

My favorite movie

On the flight home, I watched my favorite movie, The Year of Living Dangerously, starring Mel Gibson, a 1982 movie about a journalist covering the deterioration of Indonesia in 1965 under a corrupt government. There were a lot of parallels with what I was witnessing, including the last scene, where Gibson’s character escapes the madness and poverty, and heads for London. I couldn’t help but feel guilty, knowing what I was leaving behind me.

June shared with us a message from a friend in Haiti last week:  “The food and water crisis is already upon us — not so much [where we are] because we still have rice and are able to buy some beans. So the kids are still getting their one meal a day. But in the surrounding community people are already going whole days or more without food either because the markets are closed or even when the markets have food, they don’t have the money to buy it. The price of food has almost doubled since this began (and, because the value of the Haitian gourde has plummeted this year, the prices were already higher than normal).” And since then, riots have worsened in PAP, and people have been killed.

Steven’s photo in September after getting his first dose of factor: he’s walking again!

We will return to Haiti and resume; we’ve come too far and actually have a foothold now with hemophilia care. Pray for Haiti, and its people. They have suffered too much to stop now. We will continue to send factor to the boys we know. I have a registry of 11 boys with hemophilia, and am the only one who knows who they are, and where they are. I had hoped to transfer this knowledge to the local teams and start the first national registry. So I must return. And want to return.

See complete photo gallery of Haiti here.

 

 

 

 

 

 

Haiti: Little by Little

Piti, piti, wazo fe nich li. Little by little the bird builds its nest —Haitian saying.

I’ve either done a very poor job or a very good job trying to get hemophilia care to Haiti. I started in 2001, solo, trying to figure out the puzzle that is Haiti. It dawned on me in 1996, when I attended my first world congress in Ireland, that very few people from Africa or African descent were in attendance. And from that point on, I made sub-Sahara Africa and Haiti (the first free black nation!) a personal mission.

I was able to help start hemophilia societies in Ghana, Tanzania, Zambia, Uganda, and now Rwanda. I was the only one visiting Zimbabwe over a 12-year stretch. I was the first in the global community to visit Kenya, which had a society technically in 2001, but not very active. All of these national organizations, with the exception of Rwanda, which is still forming, are doing well. Kenya is doing great, in particular! I merely was a catalyst and instigator. The families and patients in the countries, and their physicians, deserve all the praise for their dedication.

But Haiti. It sits a mere 90 minutes off our coast. No one from Haiti with hemophilia and no physician from there has attended a world congress. So many have died; one I know from a tooth extraction. The only factor they get is what we have been sending through Project SHARE. We know now about 11 patients, and we have the only Haitian patient registry—not the Haitians. There is no treatment center, no one trained in hemophilia, in short, nothing.

All that is about to change.

Haiti is the poorest country in the western hemisphere, with an estimated population of over 10 million, of which 60% live below the poverty line. It has one of the worst life expectancies in the world (At my age, I’d be considered almost ready to die) It suffered a devastating earthquake in January 2010, which collapsed the country’s health care system. A World Bank report in 2017 noted that the annual per capita public health spending in Haiti is $13, compared with $781 in Cuba and $180 in the Dominican Republic.

Infectious disease is a high risk; in October 2010, the UN peacekeepers improperly disposed if human waste into Haiti’s main river system and caused a massive cholera outbreak. Cholera was new to Haiti, and over 10,000 died from it!

There has never been a national hemophilia program in Haiti. So my aim these many years has been to start the first national hemophilia program in Haiti’s history. What I needed was a hospital willing to be the center, the hub of everything hemophilia. And above all, the center to which we should ship our donated factor. Right now we are shipping to one child in an orphanage over in the west, then to another boy in the capital, Port-au-Prince, then to another boy in the northeast. Crazy! The requests have come in over the years from various healthcare workers who have been to Haiti, and found a child they think has hemophilia. We help get them tested and then send medicine.

Laurie Kelley in 2002 with school boy

The impetus started many years ago, probably about 2000, when a pastor from Haiti was visiting in the Midwest and asked for factor for two boys he knew. He contacted one of our NHF chapters, I forget which one by now, and they redirected him to me. I was torn because I had factor but just couldn’t give it to a stranger, without a physician’s oversight and approval. So the pastor went back to Haiti empty-handed. About a year later he returned, with the same request. Again I had to turn him down, but asked if I could come to Haiti to check it out, meet the boys and their doctor, to verify it. He put me in touch with the Christianville Mission group, and they invited me on their next mission trip. When I told the wife of the leader of the mission I had to see first if I could get corporate sponsorship for the trip, she immediately replied, “Maybe God wants you to pay for it yourself.” That resonated loudly. I put my own money down and before I knew it, I was going to Haiti.

That was a life-changing trip, and I had been to a few countries by then. Going to Haiti was a bit like going back in time. Unlike almost any other country, Haiti is so isolated. Surrounded by Spanish-speaking and English-speaking countries, Haitians speak Creole, and French. The are hard-working people, and long suffering. The island has been battered by hurricanes and earthquakes, and corrupt politicians.

I met the boys, and their father, who were all impressive. The father was director of a 120-employee mission compound, with 1,200 school children. He spoke English, Spanish, Creole and French! His teen boys had hemophilia, and we provided the factor. We had a great visit and I had hoped he would spearhead our efforts to start a hemophilia program, but in the following years, he emigrated to the US, to give his children a better future. And they are doing great now. I am now friends with one of the boys, now a man, on Facebook!

So I return again… this road to Haiti hemophilia care could be a book. I have four pages of contacts of people through the years who have helped, tried to help and who have left a legacy. I have voluminous notes and stories, and photos. This trip today is the culmination of all their efforts, all of our efforts.

And this time, we will succeed!

 

 

 

The Day the Music Cried

Today is the 60th anniversary of what was dubbed “The Day the Music Died,” by singer Don McClean in the song “American Pie.” The day that singer Buddy Holly, Ritchie Valens and The Big Bopper died in a plane crash in an Iowa cornfield at 1 am on a frigid morning, after performing at the Surf Ballroom. Besides the song immortalizing the young men, the movie “The Buddy Holly Story” commemorates the life of Buddy Holly, who was surely one of the most amazing and talented rising stars in his time. Great movie, with Buddy Holly spectacularly played by actor Gary Busey.

I recently watched the movie, and then read a biography on Buddy. He is undoubtedly one of my favorite musicians in rock. His talent cannot be overstated. When he died at age 22 in the crash, he was already a global sensation. He wrote and performed 50 songs, with the blockbuster “Peggy Sue” often dubbed as one of rock’s great songs. (In 1999, the song made it on the NPR 100, a list of the 100 Most Important American Musical Works of the 20th Century”) Buddy traveled the world, visiting Australia and England, where he was revered. When he performed in England, a 15-year-old Bob Dylan watched him in awe from the audience, as did a young group called the Quarrymen (later The Beatles). They were mesmerized that someone like them—a young man— could make it so big. That he wrote his own songs (singers and performers usually didn’t do that then; Elvis sure didn’t). That he started getting into production of his music. That he couldn’t even read music! His talents were natural and sharp. He created a new genre—rockabilly, combining the country-western style of his home state Texas with leading edge rock and roll.

 

 

His band was called the Crickets; different tales speculate on the origin of the name but for sure, if you listen to the song “I’m Gonna Love You Too,” you will hear a cricket chirping at the end of the track. One was in the studio and they couldn’t silence it. And it’s also true that the name the Crickets inspired another band, called the Beatles. Paul McCartney is quoted as saying, “If there hadn’t been a Buddy Holly, there would have been no Beatles.” The British group the Hollies are named for him. Weezer has a song called “Buddy Holly.” The Rolling Stones first US hit was a cover: “Fade Away” by Buddy Holly. And the Quarrymen (Beatles) first ever 45 was “That’ll Be the Day.”

Holly went on to inspire musicians for years and decades after his death. When you think of his brief life, and realize there was an amazingly small window of only 18 months from when he emerged on the music scene till his death, it’s absolutely incredible what he accomplished. And he was mentoring a young and struggling musician named Waylon Jennings, who was performing with them the night of the crash. Waylon gave up his seat to the Big Bopper (J.P. Richardson), who was suffering from the flu. None of the young men wanted to travel in the old school bus that kept breaking down, with no heat, another 10 hours to Minneapolis in the cold. Buddy chartered the plane. Waylon would suffer survivor guilt for years afterwards. The plane crashed within minutes of take off at 1 am. All four people on board were killed instantly.

The movie, often dubbed “The Buddy Hollywood Story,” is not terribly accurate. Paul McCartney, a huge fan, made a documentary about Buddy Holly, after the first movie, to set the record straight. (And he bought the entire catalogue of Buddy Holly songs.) Unlike how he is portrayed in the movie, Buddy wasn’t arrogant, never tried to punch anyone. As a Texan Baptist he was polite, and incredibly creative.

 

 

What does all this have to do with hemophilia? Nothing, except our community has so many young talented musicians, waiting for their chance. Buddy’s story is inspiring—I highly recommend reading Buddy Holly: A Biography by Ellis Amburn. And listen to his music: it’s magical, uplifting, clever, innovative. Buddy made it cool to wear glasses (John Lennon, very visually challenged, took to wearing his specs on stage after seeing Buddy). Buddy made it cool to look like a geek and be a star. He never doubted himself a second, and I hope our young stars never do either.

Dust off your guitar and send your music to Blood Vibrations (https://bloodvibrations.bandcamp.com/), a group from our community, which will promote your music on their website and in their album. They’re waiting for you.

And Rave On!

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