Talia Duff has a rare form of Charcot-Marie Tooth disease (as well as trisomy 21 Down syndrome), with her mom Jocelyn.
As Mother’s Day and the annual meeting of the American Society of Gene and Cell Therapy approach, I’d like to update the stories of some of the moms I’ve written about, and introduce a new friend with perhaps the most astonishing gene therapy experience of all.
These women are some of the pioneers whose efforts will bring gene therapy to many more families. I wrote about Lori and Ilyce in my book The Forever Fix: Gene Therapy and the Boy Who Saved It, and met the others when they contacted me after reading it.
Jocelyn
Jocelyn Duff, executive director of CureCMT4J, is mom to Talia, who has a very rare form of Charcot-Marie-Tooth (CMT) syndrome, as well as trisomy 21 Down syndrome. DNA Science told her story for Rare Disease Day 2017. Jocelyn updates:
"Our research at The Jackson Laboratory has shown incredible success using gene therapy in mice. Additionally, we’ve secured a spot in a manufacturing queue, are working with researchers on our pre-IND (investigational new drug application with FDA), and hope to reach a clinical trial in early 2019. In 18 months we moved from the first-ever meeting of scientific investigators addressing an expedited path toward treatment or cure for CMT4J, to proof-of-concept in our preclinical work, raising over $1 million towards a gene therapy.
While it seems that we’ve accomplished so much, so quickly, it feels glacially slow as I watch the continued onslaught of this disease in Talia. She’s now in a wheelchair, has lost most of the use of her arms, and requires daily respiratory therapies. Despite the progression, Talia remains her sweet, funny, smart self. She’s resilient and resourceful, coming up with new ways to adapt to her ever-changing world every day."
When Talia’s school reported a new “habit” of sucking her finger, it turned out that she was grabbing a finger with her mouth to hoist her arm up onto a table. Last year, her classmates and teachers created a video that propelled CureCMT4J towards their $1 million goal. “Our little community has embraced Tal and our fight. It’s been extraordinary,” Jocelyn says.
Kristin
Like Jocelyn Duff, Kristin Smedley is a tireless champion of gene therapy, trying to get a clinical trial up and running to treat her family’s form of retinal blindness, boosted by the FDA approval in late 2017 of Luxturna, to treat a similar condition.
In 2014, I watched Kristin’s elder son Michael belt out “Born to Run” in a packed ballroom at the "Cocktails for the Cure," the annual fundraiser for the Cure Retinal Blindness Foundation. The initials echo the name of the gene, CRB1, that has taken the vision from Michael and his younger brother Mitchell.
Later that evening, Michael joined Christian Guardino onstage to play “Don’t Stop Believing.” The crowd didn’t know it, but Christian had recently undergone gene therapy for the blindness that Luxturna treats. Christian went on to win America’s Got Talent.
Kristin founded CRBF, which will hold its sixth research conference at the Cold Spring Harbor Laboratory at summer’s end. And she hopes that gene therapy will one day conquer her family’s mutant gene. “Gene therapy is the best hope for my boys. Even if it only restores a fraction of vision, that could mean no longer needing a cane to navigate or being able to read print instead of Braille,” Kristin wrote in a guest post for Rare Disease Day 2014.
Michael has soared, as a musician, an actor, and an athlete. And now Kristin is preparing for a maternal milestone: sending him off to college.
“Michael is getting ready for his senior prom and graduation. He was accepted to his top choices of colleges to pursue a career in Music Business – Belmont University (Nashville) and Berklee College of Music (Boston). He also made the waitlist for Harvard and will find out the outcome of acceptance in June!
Younger brother Mitchell is wrapping up freshman year of high school with a bang – he is a top 10 finalist in the country for his age bracket in the National Braille Challenge! He goes to LA in June to compete in the finals,” Kristin says.
Lori
Parents of kids in clinical trials, especially for something as unprecedented as gene therapy, must take care in describing what they may or may not see in their children. It’s human nature to note progress, but disease progression, not so much. Researchers prefer that parents say as little as possible while a study is ongoing, so as not to raise hopes too soon.
And so Lori Sames isn’t free to comment about how her daughter Hannah is doing since her gene therapy for giant axonal neuropathy (GAN) in July 2016 at the National Institutes of Health, except to say she “is doing great! She continues to gain strength” through physical therapy and exercise. Hannah’s face right before the 8th grade semi-formal last week is worth many words.
Hannah’s story is chronicled here. As more children are treated for GAN, some with higher doses, research continues on finding ways to deliver the gene more efficiently, either by packing more healing DNA into the viral vectors, or upping the dose. Effects of certain drugs on progress post-gene therapy are also under investigation.
Cara
Cara O’Neill, a pediatrician, is mom to Eliza, who received gene therapy for Sanfilippo syndrome (aka mucopolysaccharidosis Type IIIA) two years ago (See ""Eliza Gets Her Gene Therapy"). Cara and her husband Glenn, along with big brother Beckham, kept Eliza isolated for 722 days so she wouldn’t contact the type of virus used as a vector in the gene therapy protocol at Nationwide Children’s Hospital in Columbus, Ohio. Infection might have disqualified her.
Like Lori Sames, Cara can’t say much, but this video shows how Eliza has relearned to use a fork — a task requiring fine hand-eye (and mouth) coordination
Reports Cara:
"Eliza has been enjoying lots of things lately. She loves the pool, especially a lazy river, which for her is not very lazy as she jumps along the whole way. She loves amusement rides. Splash Mountain is her favorite. Everyday activities are special too – getting a haircut, going for a walk in the woods. I will always have hope for my sweet girl that these are things we will get to do together for a very long time. Mother’s Day always takes on an extra special meaning, and I’m the luckiest mom in the world to have Eliza and Beckham."
Ilyce
Gene therapies have been in clinical trials since 1990. Ilyce Randell is in that sense a veteran – her son, Max, received gene therapy for Canavan disease twice, as an infant and toddler. Canavan is a neurodegenerative disease that takes away movement but spares the intellect – Max has done very well in school.
Max wasn’t expected to see his eighth birthday, but in October, he will turn 21! If there were a Brother’s Day, I would surely honor Max’s brother Alex, future neuroscientist. (See "A Brother’s Love Fights Genetic Disease".) Ilyce founded Canavan Research Illinois.
Sharon
Taylor King was born in August, 1998. Charming and precocious, she was the first to learn to read in preschool, recalls her sister Laura King Edwards. But by first grade, Taylor started to lose math skills. “There were signs of the secret hiding in Taylor’s genes even then,” Laura writes in her book, Run to the Light, to be published in November. Laura is running a race in every state to honor Taylor.
At a state fair in 2005, when Taylor froze at the top of a narrow poorly-lit stairway, her family realized she couldn’t see. And so began the diagnostic odyssey. At first Taylor was diagnosed with retinitis pigmentosa and nonverbal learning disorder, but as she lost skills, genetic testing finally led to infantile Batten disease, aka neuronal ceroid lipofuscinosis, just before her 8th birthday. Her abilities to move and communicate would gradually diminish.
Taylor’s mom Sharon founded North Carolina Rare Disease Coalition, joined the North Carolina Rare Disease Advisory Council, served on the North Carolina newborn screening task force, and raised funds to fuel development of gene therapy for Taylor’s disease at the University of North Carolina, licensed to Abeona Therapeutics in 2016. A clinical trial is slated to begin this year.
“Kudos to the many brave families we’ve met along the way for taking a stand – for their unwillingness to accept ‘no cure.’ We took that stand the day Taylor was diagnosed with Batten disease, and we’ve never backed down. Working together, we WILL win this fight,” Sharon has said. The gene therapy will be too late to help Taylor, but it will be her legacy to have helped others.
Amy
Amy Price’s experience could be called “all of the above.” Two of her children have had successful gene therapy for a lethal brain disease, but it was only possible because their elder sister died of it.
Liviana was born in January 2008 and diagnosed with metachromatic leukodystrophy (MLD) in December 2010. MLD affects the white matter in the brain, causing progressive loss of mobility and sensation, as well as intellectual decline and, ultimately, unresponsiveness. Giovanni was born in January 2010, and his sister’s terrible diagnosis at the end of that year led to the genetic testing that revealed that he had MLD too. The two children are featured at the top of this post.
Giovanni was accepted into a clinical trial in Italy for gene therapy, but it was too late for Liviana. Giovanni was treated in 2011; Liviana passed away in 2013. Amy’s blog Liviana’s (and Giovanni’s) Journey tells their story. But there’s a lot more.
In 2014 Amy had triplets. One of them, Cecilia, inherited MLD and had the gene therapy at 9 months. Only two of Amy and Brad’s 8 children have no mutations – Mendel’s first law at work.
Alessandra Biffi, MD, then at the San Raffaele Telethon Institute for Gene Therapy in Milan, headed the clinical trial; she’s now at the Harvard Stem Cell Institute. The gene therapy adds corrected genes for the enzyme arylsulfatase A to bone marrow stem cells taken from the children. The cells are infused and migrate to the brain, where they give rise to corrected glial cells that make the needed enzyme. Done early enough, symptoms never begin.
The gene therapy so far seems to stops the disease in its tracks, and teamed with newborn screening could one day prevent the suffering. The final line of the paper in The Lancet reporting the clinical trial results honors the older siblings: “In memory of Baily, Valentina, Carlos, Dennis, Liviana, Mustafa, Randa, and Amany.”
Amy, a psychologist, and Brad, a home remodeler, faced criticism of their decision to forego prenatal testing when they accidentally conceived the triplets after knowing they carried MLD, following media coverage of their situation. The wrenching experience has led Amy to pursue a graduate degree in bioethics. Amy updates:
"Giovanni is 7 years post-transplant, and Cecilia 3.5 years. He’s intuitive and caring. He’ll be the first to ask how your day was, or offer help on a challenging task. He’s enormously creative. He loves to learn what Brad is working on, so he can try to do a mini-lego version. Physically, he doesn’t have any challenges. He plays basketball and soccer and will be starting piano soon.
Cecilia almost always has a ball at her feet or in her hand and jumps right in and joins her siblings at soccer and basketball. She exceeds her triplet siblings physically and is always on the go. She’s slightly mischievous, looking for boundaries she can push."
Like the other moms, Amy’s children’s genetic illness has turned her life around in a way that will help others.
"I want to increase access to life-saving treatments for MLD and other rare diseases." She wants to end the telling parents of a newly-diagnosed child “there is nothing we can do." "There’s always something we can do. I am hopeful that the academic path I’m going down will add the method to the madness that has been MLD in our lives, and the lives of all MLD families, with the goal of easing the burden, answering the questions, and not having to bury more children. I am continually driven by Liviana’s life and the gifts she has shown me through her spirit, grace, strength, and sacrifice."
Happy Mother’s Day to Jocelyn, Kristin, Lori, Cara, Ilyce, Sharon, and Amy, and the many other incredible moms making gene therapy possible whom I haven’t yet met. Please get in touch and share your stories!
This post first appeared at my blog DNA Science at Public Library of Science.
These women are some of the pioneers whose efforts will bring gene therapy to many more families. I wrote about Lori and Ilyce in my book The Forever Fix: Gene Therapy and the Boy Who Saved It, and met the others when they contacted me after reading it.
Jocelyn
Jocelyn Duff, executive director of CureCMT4J, is mom to Talia, who has a very rare form of Charcot-Marie-Tooth (CMT) syndrome, as well as trisomy 21 Down syndrome. DNA Science told her story for Rare Disease Day 2017. Jocelyn updates:
"Our research at The Jackson Laboratory has shown incredible success using gene therapy in mice. Additionally, we’ve secured a spot in a manufacturing queue, are working with researchers on our pre-IND (investigational new drug application with FDA), and hope to reach a clinical trial in early 2019. In 18 months we moved from the first-ever meeting of scientific investigators addressing an expedited path toward treatment or cure for CMT4J, to proof-of-concept in our preclinical work, raising over $1 million towards a gene therapy.
While it seems that we’ve accomplished so much, so quickly, it feels glacially slow as I watch the continued onslaught of this disease in Talia. She’s now in a wheelchair, has lost most of the use of her arms, and requires daily respiratory therapies. Despite the progression, Talia remains her sweet, funny, smart self. She’s resilient and resourceful, coming up with new ways to adapt to her ever-changing world every day."
When Talia’s school reported a new “habit” of sucking her finger, it turned out that she was grabbing a finger with her mouth to hoist her arm up onto a table. Last year, her classmates and teachers created a video that propelled CureCMT4J towards their $1 million goal. “Our little community has embraced Tal and our fight. It’s been extraordinary,” Jocelyn says.
Kristin
Like Jocelyn Duff, Kristin Smedley is a tireless champion of gene therapy, trying to get a clinical trial up and running to treat her family’s form of retinal blindness, boosted by the FDA approval in late 2017 of Luxturna, to treat a similar condition.
In 2014, I watched Kristin’s elder son Michael belt out “Born to Run” in a packed ballroom at the "Cocktails for the Cure," the annual fundraiser for the Cure Retinal Blindness Foundation. The initials echo the name of the gene, CRB1, that has taken the vision from Michael and his younger brother Mitchell.
Later that evening, Michael joined Christian Guardino onstage to play “Don’t Stop Believing.” The crowd didn’t know it, but Christian had recently undergone gene therapy for the blindness that Luxturna treats. Christian went on to win America’s Got Talent.
Kristin founded CRBF, which will hold its sixth research conference at the Cold Spring Harbor Laboratory at summer’s end. And she hopes that gene therapy will one day conquer her family’s mutant gene. “Gene therapy is the best hope for my boys. Even if it only restores a fraction of vision, that could mean no longer needing a cane to navigate or being able to read print instead of Braille,” Kristin wrote in a guest post for Rare Disease Day 2014.
Michael has soared, as a musician, an actor, and an athlete. And now Kristin is preparing for a maternal milestone: sending him off to college.
“Michael is getting ready for his senior prom and graduation. He was accepted to his top choices of colleges to pursue a career in Music Business – Belmont University (Nashville) and Berklee College of Music (Boston). He also made the waitlist for Harvard and will find out the outcome of acceptance in June!
Younger brother Mitchell is wrapping up freshman year of high school with a bang – he is a top 10 finalist in the country for his age bracket in the National Braille Challenge! He goes to LA in June to compete in the finals,” Kristin says.
Lori
Parents of kids in clinical trials, especially for something as unprecedented as gene therapy, must take care in describing what they may or may not see in their children. It’s human nature to note progress, but disease progression, not so much. Researchers prefer that parents say as little as possible while a study is ongoing, so as not to raise hopes too soon.
And so Lori Sames isn’t free to comment about how her daughter Hannah is doing since her gene therapy for giant axonal neuropathy (GAN) in July 2016 at the National Institutes of Health, except to say she “is doing great! She continues to gain strength” through physical therapy and exercise. Hannah’s face right before the 8th grade semi-formal last week is worth many words.
Hannah’s story is chronicled here. As more children are treated for GAN, some with higher doses, research continues on finding ways to deliver the gene more efficiently, either by packing more healing DNA into the viral vectors, or upping the dose. Effects of certain drugs on progress post-gene therapy are also under investigation.
Cara
Cara O’Neill, a pediatrician, is mom to Eliza, who received gene therapy for Sanfilippo syndrome (aka mucopolysaccharidosis Type IIIA) two years ago (See ""Eliza Gets Her Gene Therapy"). Cara and her husband Glenn, along with big brother Beckham, kept Eliza isolated for 722 days so she wouldn’t contact the type of virus used as a vector in the gene therapy protocol at Nationwide Children’s Hospital in Columbus, Ohio. Infection might have disqualified her.
Like Lori Sames, Cara can’t say much, but this video shows how Eliza has relearned to use a fork — a task requiring fine hand-eye (and mouth) coordination
Reports Cara:
"Eliza has been enjoying lots of things lately. She loves the pool, especially a lazy river, which for her is not very lazy as she jumps along the whole way. She loves amusement rides. Splash Mountain is her favorite. Everyday activities are special too – getting a haircut, going for a walk in the woods. I will always have hope for my sweet girl that these are things we will get to do together for a very long time. Mother’s Day always takes on an extra special meaning, and I’m the luckiest mom in the world to have Eliza and Beckham."
Ilyce
Gene therapies have been in clinical trials since 1990. Ilyce Randell is in that sense a veteran – her son, Max, received gene therapy for Canavan disease twice, as an infant and toddler. Canavan is a neurodegenerative disease that takes away movement but spares the intellect – Max has done very well in school.
Max wasn’t expected to see his eighth birthday, but in October, he will turn 21! If there were a Brother’s Day, I would surely honor Max’s brother Alex, future neuroscientist. (See "A Brother’s Love Fights Genetic Disease".) Ilyce founded Canavan Research Illinois.
Sharon
Taylor King was born in August, 1998. Charming and precocious, she was the first to learn to read in preschool, recalls her sister Laura King Edwards. But by first grade, Taylor started to lose math skills. “There were signs of the secret hiding in Taylor’s genes even then,” Laura writes in her book, Run to the Light, to be published in November. Laura is running a race in every state to honor Taylor.
At a state fair in 2005, when Taylor froze at the top of a narrow poorly-lit stairway, her family realized she couldn’t see. And so began the diagnostic odyssey. At first Taylor was diagnosed with retinitis pigmentosa and nonverbal learning disorder, but as she lost skills, genetic testing finally led to infantile Batten disease, aka neuronal ceroid lipofuscinosis, just before her 8th birthday. Her abilities to move and communicate would gradually diminish.
Taylor’s mom Sharon founded North Carolina Rare Disease Coalition, joined the North Carolina Rare Disease Advisory Council, served on the North Carolina newborn screening task force, and raised funds to fuel development of gene therapy for Taylor’s disease at the University of North Carolina, licensed to Abeona Therapeutics in 2016. A clinical trial is slated to begin this year.
“Kudos to the many brave families we’ve met along the way for taking a stand – for their unwillingness to accept ‘no cure.’ We took that stand the day Taylor was diagnosed with Batten disease, and we’ve never backed down. Working together, we WILL win this fight,” Sharon has said. The gene therapy will be too late to help Taylor, but it will be her legacy to have helped others.
Amy
Amy Price’s experience could be called “all of the above.” Two of her children have had successful gene therapy for a lethal brain disease, but it was only possible because their elder sister died of it.
Liviana was born in January 2008 and diagnosed with metachromatic leukodystrophy (MLD) in December 2010. MLD affects the white matter in the brain, causing progressive loss of mobility and sensation, as well as intellectual decline and, ultimately, unresponsiveness. Giovanni was born in January 2010, and his sister’s terrible diagnosis at the end of that year led to the genetic testing that revealed that he had MLD too. The two children are featured at the top of this post.
Giovanni was accepted into a clinical trial in Italy for gene therapy, but it was too late for Liviana. Giovanni was treated in 2011; Liviana passed away in 2013. Amy’s blog Liviana’s (and Giovanni’s) Journey tells their story. But there’s a lot more.
In 2014 Amy had triplets. One of them, Cecilia, inherited MLD and had the gene therapy at 9 months. Only two of Amy and Brad’s 8 children have no mutations – Mendel’s first law at work.
Alessandra Biffi, MD, then at the San Raffaele Telethon Institute for Gene Therapy in Milan, headed the clinical trial; she’s now at the Harvard Stem Cell Institute. The gene therapy adds corrected genes for the enzyme arylsulfatase A to bone marrow stem cells taken from the children. The cells are infused and migrate to the brain, where they give rise to corrected glial cells that make the needed enzyme. Done early enough, symptoms never begin.
The gene therapy so far seems to stops the disease in its tracks, and teamed with newborn screening could one day prevent the suffering. The final line of the paper in The Lancet reporting the clinical trial results honors the older siblings: “In memory of Baily, Valentina, Carlos, Dennis, Liviana, Mustafa, Randa, and Amany.”
Amy, a psychologist, and Brad, a home remodeler, faced criticism of their decision to forego prenatal testing when they accidentally conceived the triplets after knowing they carried MLD, following media coverage of their situation. The wrenching experience has led Amy to pursue a graduate degree in bioethics. Amy updates:
"Giovanni is 7 years post-transplant, and Cecilia 3.5 years. He’s intuitive and caring. He’ll be the first to ask how your day was, or offer help on a challenging task. He’s enormously creative. He loves to learn what Brad is working on, so he can try to do a mini-lego version. Physically, he doesn’t have any challenges. He plays basketball and soccer and will be starting piano soon.
Cecilia almost always has a ball at her feet or in her hand and jumps right in and joins her siblings at soccer and basketball. She exceeds her triplet siblings physically and is always on the go. She’s slightly mischievous, looking for boundaries she can push."
Like the other moms, Amy’s children’s genetic illness has turned her life around in a way that will help others.
"I want to increase access to life-saving treatments for MLD and other rare diseases." She wants to end the telling parents of a newly-diagnosed child “there is nothing we can do." "There’s always something we can do. I am hopeful that the academic path I’m going down will add the method to the madness that has been MLD in our lives, and the lives of all MLD families, with the goal of easing the burden, answering the questions, and not having to bury more children. I am continually driven by Liviana’s life and the gifts she has shown me through her spirit, grace, strength, and sacrifice."
Happy Mother’s Day to Jocelyn, Kristin, Lori, Cara, Ilyce, Sharon, and Amy, and the many other incredible moms making gene therapy possible whom I haven’t yet met. Please get in touch and share your stories!
This post first appeared at my blog DNA Science at Public Library of Science.