September 26, 2018

Sickle cell disease affects more than 100,000 Americans and millions more worldwide. This red blood cell disorder can be treated, but a widely available cure has yet to be found. Texas Children’s hematologist and Assistant Professor of Pediatrics Dr. Vivien Sheehan has recently developed a new sickle cell treatment based on her laboratory research. Sheehan has found that metformin, a commonly used medication for diabetes, has the ability to induce fetal hemoglobin in developing red blood cells.

Since higher levels of fetal hemoglobin reduce sickling in red blood cells of patients with sickle cell disease, the medication could potentially be useful in reducing the severity of sickle cell complications in patients. It also can be taken with another drug that increases fetal hemoglobin, hydroxyurea, to get even more clinical benefit.

Sheehan has been a part of Texas Children’s Cancer Center faculty since 2012, working tirelessly toward advancing sickle cell treatments. During a cancer related conference she attended, it was mentioned that the drug metformin could help with cancer by increasing amounts of proteins that her research showed increased fetal hemoglobin. This led Sheehan to wonder if the drug would increase fetal hemoglobin in cells from patients with sickle cell disease, and sure enough, it did.

“Because metformin is so well studied, so safe, there are millions of people literally taking it,” Sheehan said. “I then went to my Institutional Review Board (IRB) and asked if I could start a clinical trial of metformin in sickle cell patients since it was known to be safe, and wouldn’t cause hypoglycemia even in non-diabetics.”

With funding from Pfizer, in 2016 Sheehan and other researchers were able to launch a clinical trial that is currently assessing the effectiveness of metformin to make fetal hemoglobin in patients with sickle cell cared for here at Texas Children’s Hospital Hematology Center. Pfizer is a world leader in global medical advancement that provides medical research grants and scholarships for new drug development and the latest in cutting edge technology and applications. This not only led to developing the clinical trial, but also led to other acknowledgements and funding such as Sheehan’s Best of ASH recognition, given by the American Society of Hematology at the 2016 annual meeting.

“Her passion truly exudes from her and so a lot of times when you get into conversation with her, you always leave so much more educated because she’s letting you know the newest things that she has learned,” said nurse practitioner Precious Uwaezuoke. “She’s letting you know how her research studies are going. Thus, hearing her speak is always so rewarding and fun. I truly have this huge respect for her just because of how passionate she is about Sickle Cell Disease and our kids.”

Uwaezuoke works closely with Sheehan and the research team, as well as patients, and is responsible for helping to determine who may be good candidates for clinical trials. Fighting sickle cell herself, she knows that at times handling the disease can be very difficult; so she verses how important research is to getting closer to finding a cure for the disease.

“This is a big deal because having sickle cell is not easy. It affects way too many people for us to only have developed one therapy 20 years ago,” Uwaezuoke said. “To be able to see something come to fruition like this because somebody had a dream, and chased it and didn’t let it fall to the wayside is exciting. Anytime somebody wins after trying a therapy and it actually helps them, I feel like I won as well.”

Following the clinical trial, the next step will be commercialization. Sheehan says that the progress is very exhilarating and that it is amazing for a process of this magnitude to have been executed in just four years.

“Usually it takes around 15 years,” Sheehan said. “That’s the average time it takes to develop a drug from the bench to the bedside, and that’s a pharmaceutical company with all of their staff. So now we’re in 2018, we’re almost done with the first arm of our clinical trial, patients taking both hydroxyurea and metformin, and can now analyze and publish our results.”

Overall, preliminary research results show fetal hemoglobin induction, the repair of blood vessels, which is so important to help prevent complications of stroke, retinopathy, renal failure, and the other issues that cause a lot of damage or even death to some patients with sickle cell disease.

“Ultimately, I needed to determine whether patients were having more pain crises or less pain crises on metformin and whether they’re needing more transfusions or fewer transfusions”, Sheehan said. “So I compared the time period before they started the drug to the time period on metformin and they were having fewer pain crises and they were needing fewer transfusions.”

Sheehan says that research is key to improving the use of the tools that we already have. She is now looking for a few more participants to complete the second arm of the clinical trial, patients not on hydroxyurea, and also add adult patients up to the age of 40 years. Sheehan has formed a collaboration with University of Texas Health Sciences Center’s Comprehensive Sickle Cell Center and Dr. Juneja and Dr. Idowu to be able to enroll these patients.

“It’s the only way to advance in a meaningful way. You can make incremental advances just by improving access to care or use of the drug, but you’re not going to make a big, significant change without research. Those with Sickle Cell are doing better through childhood, but they’re still not living longer in adulthood and I think it’s the lack of therapies that will continue to work in our older patients and I feel like this is going to be one of them and I want to see it improve life spans and not just number of years, but health.”

July 3, 2018

For the second consecutive year, Texas Children’s Sickle Cell Center hosted a celebration in honor of World Sickle Cell Day. On June 19, sickle cell patients, families, physicians, researchers and others joined forces to raise awareness about sickle cell disease, an inherited red blood cell disorder that affects about 100,000 Americans and many more worldwide.

Held at Texas Children’s Pavilion for Women, the celebration began with a greeting from one of Texas Children’s Hospital’s most friendly employees, Elsa, one of three therapy dogs who helps comfort patients during their stay at the hospital.

Notable presentations, given by Texas Children’s faculty, reviewed the historical considerations of sickle cell and advancements in care and therapies.

“Our team is doing a great job developing drug strategies, but we do have room to grow,” said Dr. Donald Mahoney Jr., director of Texas Children’s Hematology Center. “Our goal is to make sure the disease is no longer progressive and debilitating.”

Dr. Alex George, co-director of Texas Children’s Sickle Cell Center, highlighted four elements that are essential to Texas Children’s methodology of helping reverse this outlook: patient care, education, research and advocacy. Texas Children’s has been at the forefront of the fight against sickle cell disease for decades, screening newborns for the disease since the 1950s. Since 2011, these efforts have been expanded globally to Africa, where many more people suffer from the disease and screening and treatment are limited.

Texas Children’s is now treating children with sickle cell disease in Angola, Malawi, Uganda, Botswana, and other areas of Sub-Saharan Africa as well as training local physicians to do the same. Dr. Parth Mehta, Director of the Global Oncology Program, and Dr. Peter Wasswa, Director of Hematology for the Global HOPE Hematology/Oncology Pediatric Excellence) Program in Uganda, discussed the various milestones of the programs including the estimated 245,000 babies who have been screened with about one in 65 having sickle cell disease.

Another memorable aspect of this year’s ceremony were the family experiences which reflected on the Center’s individualized course of treatment including patient care, education, psychosocial support services, screening and counseling for children and their families. Serving more than 1,100 children each year, Texas Children’s Sickle Cell Center is one of the largest in Texas, offering the latest treatments including hydroxyurea, transfusions and stem cell transplantation.

Uduak Ekaette and her 15-year-old son have experienced sickle cell care in a low-resource setting having lived in Nigeria, West Africa, and he now receives treatment at the Sickle Cell Center which she describes as a place of hope.

“I really have been blessed in unmeasurable ways by my interactions with the staff at Texas Children’s Hospital,” Ekaette said. “Our experience has been fantastic.”

Maya Cooper, mother of a sickle cell patient, said her family also has had a great experience at Texas Children’s Sickle Cell Center.

“They always strive to keep us in the loop, keep us educated about what’s going on,” Cooper said. “I feel like we can give our input into decision-making, which is a big deal.”

The Coopers moved from San Antonio to be close to family and friends and to receive treatment at Texas Children’s. Cooper’s husband, Ishmael, said their goal is to have their child with sickle cell disease live a normal life.

“Although it is really hard, we do it,” he said. “And it’s all because of Texas Children’s Hospital.”

The Sickle Cell Center also collaborates with organizations across the region to help educate people about sickle cell disease and advocate for a cure. Partners of the Sickle Cell Center that were present during the celebration were; The Periwinkle Foundation, Sickle Cell Association of Texas Marc Thomas Foundation, As One Foundation, Novartis Hematology, and Supporting Our Sicklers (SOS). Each organization provided educational information about sickle cell disease or trait. The Houston Health Department also was present to discuss the importance of newborn screening, improving access to care, and ultimately resolving the health disparity issue.

“We are really fortunate here at Texas Children’s to be able to provide such dedicated care,” said Dr. Amber Yates, co-director of Texas Children’s Sickle Cell Center. “We have a large team which focuses solely on children with sickle cell disease. Our hope is that this event will grow more each year.”

To end the celebration, attendees were able to view a portion of the Texas Children’s Ugandan World Sickle Cell Day Ceremony which featured a song and dance rendered by children. The song’s lyrics aptly captured the spirit of the day – “…let’s come together in the fight for sickle cell!”

Click here to read a blog by Jamilah Cummings, the mother of Joshua, a patient sickle cell disease at Texas Children’s Hospital.

To learn more about Texas Children’s Sickle Cell Center click here.