MUSC researchers make strong advances toward better sickle cell treatments

More than 4,000 people in South Carolina, most of African descent, suffer from a life-limiting genetic disorder called sickle cell disease (SCD) that causes red blood cells to mutate and stop doing their primary task: delivering oxygen to vital organs. Historically, awareness of this disease has lagged far behind other genetic diseases, and research and treatment options have been underfunded. 

Now, thanks to more than $11 million in National Institutes of Health funding and a handful of passionate providers, researchers at the Medical University of South Carolina are making strong advances toward better treatments and cures for this painful disorder. 

 

Until the past decade, children with SCD often spent their days worrying about when they would get too sick to function. Their families had to treat every fever as though it were life-threatening. Even on days when the children felt well, the specter of pain that impedes regular life was lurking in the back of their minds.

“To grow up that way as a child, you can imagine what is it like…to be thinking about your health, you know, every day, and worrying about it, and that’s the nature of the disease; there’s no predictability,” said Sherron Jackson, M.D., the recently retired director of the pediatric sickle cell program.

These worries were very real. A sickle cell disease episode would disrupt their lives without warning, causing them to miss out on school or church or social activities. Acute bone pain would often last several days. There was always a chance of suffering a stroke caused by clumps of sickle-shaped blood cells in the brain or trouble breathing when blocked blood flow to the lungs can’t bring enough oxygen in. They were little ones with big worries, and their doctors couldn’t do much about it beyond treating the symptoms. 

Sickle cell disease is a blood disorder most commonly found in populations of African or Middle Eastern descent. More than 100,000 people nationwide have the genetic mutation, which causes hemoglobin blood cells to change to a sickle shape, like a quarter moon, and bunch in the vessels and organs, causing acute pain and tissue damage and increasing risk for strokes. 

Researchers and providers at MUSC began confronting the life-limiting fear, pain and physical damage caused by SCD with an arsenal of new weapons, starting in the early 1980s. Today, babies born with sickle cell have several hopeful alternatives for a bright and healthy future. 

Early steps

Starting in 1981, MUSC doctors introduced three life-saving steps in diagnosing and treating children with SCD: infant screening for the disease at birth, prophylactic penicillin treatments and, later, a painless and effective screening called transcranial doppler for preventing strokes in children with sickle cell disease. 

Learning early that a baby has sickle cell helps doctors to take precautions like starting penicillin, preventing life-threatening infections. 

“Sickle cell children were dying from pneumococcal sepsis. They had a fever, and you didn’t even know what was wrong,” said Jackson, who spent her career caring for children and families with SCD. “Those early deaths were devastating because they could have been prevented if children were screened for sickle cell disease at birth.” 

Undiagnosed babies are at risk for infections as well as pain crises, which are different in children than in adults. They can’t tell you what’s going on with them, said Jackson. But their bodies will tell you. When babies have pain crises, they have hand and foot swelling, and “their fingers are swollen like little sausages,” she said. In older children, they just say, ‘The arm hurts; the legs hurt,’ and in adults, the sternum and the low back will hurt. 

 

In 1981, Jackson and colleagues received a grant to do sickle cell testing at MUSC. For two years, they tested all newborns, regardless of race, for SCD. The research found that nearly 100 babies tested positive for sickle cell and established newborn screening for SCD as standard of care in South Carolina. 

Just a tiny drop of blood from every newborn’s heel gave providers the information they needed to start not only penicillin to prevent dangerous infections but also education for sickle cell babies and families. 

Since the mid-1990s, part of that education included emphasizing to families the importance of yearly screening for stroke risk using transcranial doppler on all children diagnosed with severe forms of SCD, also called sickle cell anemia. 

“This was started by Dr. Robert F. Adams, who was in Augusta at the time. His technique was to use a doppler ultrasound like we do for pregnancy, and he discovered that we can put a doppler on the temple by each side and measure the blood flow in the blood vessels in the brain,” Jackson said.

Now accepted as standard of care, transcranial doppler screening tells providers when a child has a high risk for stroke so they can start giving regular stroke-preventing blood transfusions. 

In 2017, the Federal Drug Administration approved for use in children a medication called hydroxyurea that could stop the sickling process before the damage to organs could even begin. It was first approved for use in adults nearly two decades earlier.

“We try to start all of our patients [who have severe forms of sickle cell] on hydroxyurea starting at nine months of age,” said MUSC pediatric hematologist Christina Abrams, M.D. 

While hydroxyurea does have side effects, and it must be taken every day for the rest of the patient’s life, this powerful medication has changed the way doctors hold SCD in check. Along with newborn screenings and transcranial doppler testing, hydroxyurea gives many sickle cell patients the chance to be children, without fear of pain, who grow up to lead healthy, productive lives. 

Now, with the introduction of additional drug therapies for sickle cell, including voxelotor, which is approved for children age 4 and older, providers have options for those who don’t tolerate hydroxyurea well, with more exciting developments on the way.   

What’s next?

A baby born with sickle cell today has more options than those born just a decade ago. 

Right now,  it is still a disease that must be managed, beginning with  a newly diagnosed infant starting prophylactic penicillin under the care of a pediatrician. Then a specialist in hematology will help sickle cell patients to manage their disease with one of the drug therapies on the market now, often starting before the child’s first birthday. 

In the near future, more sickle cell patients could possibly have a very real chance of receiving a cure. Bone marrow transplants are already available to some patients who have an exact match –usually a biological sibling. But the procedure carries risks. 

Sickle cell patient Alaysia Soles, 22, knows the risks, but is eager for her chance at a cure. “They say it will take a year of my life, with being in the hospital, with the chemo, but after the transplant, they want me to keep close … just in case,” she said. “There’s a risk of it failing or my body attacking the donor bone marrow. You can get sick and maybe die. I’m still willing to take that risk.” 

As she points out, there are more success stories than failures with this procedure, and other options for cures are coming.

An exciting one that’s not widely available yet is gene therapy, which is in clinical trials now. It’s being tested in adults first, and if the tests show that it’s safe and effective, it could be used for some children in the years to come.

 

Currently, MUSC researchers and clinicians are continuing the work to find better treatments for SCD. Since 2022, the Rena Grant Sickle Cell Center at MUSC, led by Temeia Martin, M.D., has provided consistent care for adult sickle cell patients as she works with researchers and patients over time to improve quality of life and quality of health care. Greg Hall, M.D., an Emergency Department physician at MUSC, and researcher Shannon Phillips, Ph.D., R.N., are studying ways to give sickle cell patients better tools to manage their disease and have better health care experiences in the ED. Abrams, the pediatric hematologist, is part of a research team led by Cathy Melvin, Ph.D., School of Public Health Sciences, that is looking into what patients need for better health care outcomes and quality of life. 

They are all building on the work Jackson and her colleagues accomplished during the ‘80s and ‘90s that left a legacy of effective and promising sickle cell care for children at MUSC. That cause is now championed by Abrams at the Shawn Jenkins Children’s Hospital, where between 500 and 600 sickle cell patients from birth to age 25 go for care.

“Funding for research is low to study sickle cell disease,” said Abrams, adding that it is getting better. “Curative therapy is going to be a game changer once that is put out on a bigger scale. Offering disease modifying therapies is great but doesn’t stop a lot of the end organ damage that can occur from the disease. If we can get curative therapy in a place where we offer it to individuals before they have manifestations of the disease, then we can make their entire life less affected by the disease.”

Sickle cell patient Alaysia Soles, now in nursing school, plans to be part of this work when she graduates next year, helping patients and providers understand the disease she lives with every day.