Gene editing brings new era of hope for cure to sickle cell disease

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The first time Claudia heard of sickle cell disease, she was weeks away from giving birth to her first child, a son she would name Franser. Claudia said doctors told her blood tests showed her son was likely to be born with the genetic disorder.

Sickle cell disease is predominant among African Americans and those of African descent, but it is also common among those of South and Central American ancestry. Claudia is Honduran. Doctors told Claudia how the disease affects red blood cells, causing them to warp from healthy, round and plump to sickle or banana shapes. That distortion hinders those cells’ ability to supply major organs with oxygen, leading to a host of lifelong health complications, including lung disease, heart disease, kidney disease, stroke, frequent infections and pain crises.

But it was these words – there is no cure – that Claudia remembers most clearly.

“As soon as they explained to me that this condition has no cure, my whole world came crashing down around me,” recalled Claudia.

Her son Franser was born in 2016 with sickle cell disease as the doctors had predicted. The first two years of his life were the hardest, Claudia said, as fevers and rampant infections sent Franser frequently to emergency rooms.

Living in rural North Carolina at the time, Claudia also had a hard time finding clinics and doctors trained to treat those with sickle cell disease that could provide consistent care for Franser.

As this Honduran family struggled to cope with the debilitating impact of this genetic disorder, Dr. Mitchell Weiss was assembling and growing a team of scientists and doctors at St. Jude Children’s Research Hospital to lead the next generation of work to better understand, treat and manage the myriad and lifelong effects of sickle cell disease.

He recruited top clinicians, bone marrow transplant experts and leaders in the field of gene expression to help develop new, more effective medicines and gene editing — key areas that represent a new era of hope for a cure to sickle cell disease. St. Jude has been a leader in improving standards of care for people with sickle cell disease since its founding. The first grant the research hospital in Memphis ever received was for the study of sickle cell disease in 1958, and today, St. Jude has one of the largest sickle cell programs in the country, serving about 900 patients a year. St. Jude has been part of major advances in sickle cell disease treatment over the last 60 years and continues to explore new cutting-edge curative therapies for the disease.

When work opportunities led Claudia and her family to permanently resettle in Memphis in 2019, Claudia said she was relieved when a pediatrician referred her to St. Jude and told her about the sickle cell treatment program there. Franser, who is 7, began going to St. Jude monthly for clinic visits to constantly monitor his health and symptoms. He was given medicine to take daily that helps control the sickling of red blood cells so that he has fewer side effects from the disease.

“My child already understands his condition and takes his medications dutifully,” Claudia said. “He loves going to St. Jude because he knows he will be able to play and receive so much love; he only gets a little nervous when they draw his blood.”

Two years ago, Claudia had a daughter Kendall, who also was born with sickle cell disease. Now both siblings receive care from St. Jude.

“The most important thing for me is to see them grow, to see them play without fear, and to know that I must be strong for them,” Claudia said.

Sickle cell research at St. Jude

Claudia and her children were able to lean on research built over more than half a century at St. Jude. “Sickle cell disease has disproportionately affected communities that are underserved and have been subjected to many inequalities,” said Dr. Clifford Takemoto, M.D.,Chief of Clinical Hematology at St. Jude and Lemuel Diggs Endowed Chair in Sickle Cell Disease. He works closely with Dr. Weiss. Inequities in healthcare among marginalized minority communities are something doctors at St. Jude recognized when the hospital opened in a segregated city as the first fully integrated children’s hospital in the South, and something they have worked to correct ever since.

It’s what motivated Takemoto to leave top research institutions and hospitals in Boston and Baltimore and pursue work at St. Jude. “For someone like me who has spent my career caring for people with sickle cell disease it is really a motivating factor because these communities deserve high quality comprehensive care. And unless you really fight for progress and for things that folks need, people will be forgotten,” Takemoto said.

The new generation of research and care centers around two key areas that offer promising steps toward a “cure” for patients with sickle cell disease: gene editing and bone marrow transplants, Takemoto said.

Sickle cell disease arises from the mutation of a single gene, and scientists are using new genetic engineering technology to find ways to correct that one error so that sickling of red blood cells doesn’t occur.

Results from a recent study led by St. Jude and the Broad Institute of MIT and Harvard showed the potential benefits of using gene editing to cure genetic anemias, but there is still much work to be done before it can move beyond research models in the lab to help patients in clinics.

“The ultimate goal is that it could lead to cures with no risk and no side effects, which is perfect medicine, but that’s hard to attain right now,” said Weiss, M.D., Ph.D., chair of the St. Jude Department of Hematology.

St. Jude is involved with many clinical research studies to investigate a variety of treatments for sickle cell disease, including gene therapy and the use of medicines like hydroxyurea. This drug boosts the level of fetal hemoglobin. Studies have shown that patients with higher levels of this form of hemoglobin tend to have fewer symptoms of sickle cell disease.

St. Jude is also enhancing its bone marrow transplantation program to further improve outcomes for children with sickle cell disease. Although a bone marrow transplant is a potential “cure” for sickle cell disease, it is not an easy cure, and it has many complications. That is why St. Jude continues to research alternate approaches by creating new clinical trials, for instance, that improve the entire transplant process and identify ways to decrease transplant-related side effects in children. St. Jude also develops collaborative research partnerships with the National Institutes of Health and other institutions throughout the world.

“This is something that we couldn't have done without the help of St. Jude and our donors, because bringing together expert researchers from across the country is expensive. St. Jude donor funds are supporting this collaborative research, which advances progress more quickly than individual laboratories working in isolation, ” Weiss said. 

Sickle Cell long term study and outreach

St. Jude leads the Sickle Cell Clinical Research and Intervention Program (SCCRIP), which studies how sickle cell disease progresses over time, from childhood into adulthood, and how to improve the quality of life for sickle cell disease patients.

Through a partnership with KindVr, St. Jude is conducting clinical trials using virtual reality to help pediatric sickle cell patients manage pain crises.

St. Jude understands the educational impact of sickle cell disease for patients and families. The School Program at St. Jude has school advocacy coordinators on staff to partner with parents of children with sickle cell disease to help improve their child’s educational experience. These coordinators help educate staff at the child’s school about sickle cell disease and its impact on learning, while also providing support for parents by monitoring academic progress and working with school staff to make recommendations to improve student success in the classroom. St. Jude also is testing an app, “InCharge Health,” that helps teens with medication and appointment reminders, tracks medication history and allows them to view their medical progress.

Additionally, St. Jude has developed a skills lab and created a series of educational videos to help teens transitioning from pediatric to adult sickle cell care with everyday issues such as making appointments with an adult hematologist to understanding health insurance. This information is available to centers around the country.

Sickle Cell Global outreach

But St. Jude is not just helping alleviate the burden of sickle cell disease in the U.S.

The work has expanded globally to Nigeria, which has the largest population of sickle cell disease in the world and the highest rate of infant mortality from the disease. A major reason: the country does not have universal newborn screening as the U.S. does. In collaboration with Aminu Kano Teaching Hospital in Nigeria, St. Jude implemented a newborn screening and sickle cell outreach and awareness program. In the first year, the newborn screening program tested more than 3,000 children. St. Jude also helped establish a clinic for children with sickle cell disease under 7 years old in Kano, and now the clinic has more than 500 patients. Takemoto said some of the keys to improving outcomes globally are simple: more screening, so families of kids with the disease are aware they have it; using penicillin and vaccines to control the frequent infections they’re vulnerable to; and improving access to inexpensive drugs like hydroxyurea that help control the symptoms of sickle cell. Through these simple steps, and the leadership and collaborations provided by St. Jude, Takemoto said, the hope is that children with sickle cell disease around the world can live longer, healthier lives as the patients in the U.S. do. Healthier like Franser and Kendall in Tennessee.

Franser and Kendall

Today, Franser loves spending time with his sister and his family. He also enjoys art class in school, particularly painting. Kendall is a rambunctious toddler.

“I am very happy with them. And I am trying to be a better mother every day so they can grow and become good people,” Claudia said. “I want them to respect their bodies and know that having sickle cell is a condition that they must learn to live with wherever they are.”

Kendall and Franser’s parents say they are deeply grateful for the health care and treatments the children have received at St. Jude.

“We want to thank all the people at St. Jude who keep supporting us. They should know that they are saving kids’ lives, like my two children, who are now stronger than this condition. I truly believe that one day, they will find the cure that will allow Kendall and Franser to live their lives without fear,” Claudia said.