From Comprehensive Care to Finding Cures, Fighting Sickle Cell Disease

Blood. There’s A, B, AB, and O. And then you could say there’s C. Sickle cell disease creates red blood cells that are shaped like the letter C, resembling a farm tool called a sickle. Sickle cell disease is the most commonly inherited blood disorder. It’s passed down by parents and causes red blood cells to be malformed, hard, and sticky. They clump together and block blood flow, causing pain and depriving organs of oxygen.

Sickle cell is not an equal opportunity disease. It affects those of African American and Latinx descent at a much higher rate than others. Like young Zion.

His mom, Stella, didn’t know she carried the gene mutation for sickle cell. She found out that Zion had sickle cell disease when he was born. She was referred to Stanford Medicine Children’s Health when Zion was 4, and the family moved to the Bay Area.

“Before, we saw a hematologist and a pulmonologist separately. But at Stanford Medicine Children’s we see a huge, amazing team that takes care of him,” Stella says. “Dr. Kamdar really takes the time to listen, and Kirsten is a nurse who is like his auntie.”

Sickle cell disease causes anemia, which is a reduction in red blood cells that can leave people feeling fatigued. Other symptoms include pain throughout the body, swelling in the hands and feet, damage to the spleen that can lead to frequent infections, possible vision problems, breathing problems, sleep apnea, and delayed growth. When it is left untreated, organs can become damaged. But this doesn’t have to be the case.

“I want parents to know that with good maintenance, kids with sickle cell disease can grow up, go to school, pursue interests, get married, and have kids,” says Kirsten Mouradian, a nurse practitioner in hematology who leads care coordination at the Stanford Medicine Children’s Sickle Cell Program.  

Doctors put Zion on the right medications and regularly monitor his red blood cells and symptoms to prevent crisis. He’s happy and feeling good these days. He is a talkative, bright boy that aspires to be a journalist who interviews superheroes. He just started first grade.

“Zion is a kick. He can say the name of his medicine: hydroxyurea. He’s incredibly charming,” Mouradian says.

Comprehensive sickle cell program keeps kids feeling well

The Sickle Cell Program at Stanford Medicine Children’s surrounds each patient and family with specialists from several disciplines to care for all of their health needs—including psychological and social.

“I’m very passionate about patients feeling they have a medical home with us. We provide cutting-edge care to not only treat complications, but to also prevent them,” says Aditi Kamdar, MD. “There’s nothing more gratifying than helping children live joyful, full lives.”  

The program brings together specialists from a dizzying array of services, including general surgery, cardiology, endocrinology, gastroenterology, immunology, neurology, nephrology, pulmonology, ophthalmology, audiology, dentistry, genetics, and pain management. It supports kids as they age and mature, adjusting treatments to changing needs.  

“Care for sickle cell disease is very complex, so it’s beneficial to have targeted providers see patients. We coordinate visits so parents don’t miss a lot of work and kids don’t miss school,” Mouradian says.

Stella couldn’t be happier with her son’s care. She’s extremely grateful to Stanford Medicine Children’s for helping stabilize Zion’s health so that he can be a regular kid. Maybe Zion says it best: “I like the doctors. They are nice. I like the food at the hospital, watching movies, and playing in the playroom.”

Raising awareness to activate change

Beyond providing comprehensive services, Stanford’s Sickle Cell Program leaders are also active in advocating for funding and awareness on state and national levels. For World Sickle Cell Day in June, Mouradian organized teen patients with sickle cell to write letters to their representatives in Congress asking them to support funding measures for the disease. The program is also working toward developing a regional sickle cell collaborative.

Parents of children with sickle cell disease can make change simply by advocating for their kids. Dr. Kamdar says that Stella is a wonderful mom because she’s passionate about understanding the disease and making sure Zion doesn’t feel different from his peers.

“I want people to be aware of sickle cell disease. I’d love to see a clinic created in Africa, where I grew up. Mothers need support, and they need to know whether or not they carry the sickle cell gene. Having a child with sickle cell disease changes your life,” Stella says. “I wouldn’t have a second child without knowing there was a cure.”

Exploring cures for sickle cell disease

Currently, the only definitive treatment for sickle cell disease is stem cell transplantation. Yet locating a matched donor is challenging—especially for patients of African American and Latinx descent. Traditionally, performing a transplant without a well-matched donor increases the risk of graft-versus-host disease, when the donor’s cells attack the transplant recipient’s body.

However, physician-scientists at Lucile Packard Children’s Hospital Stanford are broadening the stem cell transplant donor pool with haploidentical transplants—meaning the donor doesn’t have to be an exact match. Doctors take a sample of cells from a partially matched donor—such as a family member—and eliminate certain cells (alpha/beta T cells) to reduce the risk of graft-versus-host disease. Packard Children’s is one of the first hospitals in the Bay Area to offer this innovative stem cell transplant. Alice Bertaina, MD, PhD, a worldwide pioneer in this type of stem cell transplantation, is leading the hospital’s efforts. Other Stanford researchers and doctors are also working to make stem cell transplantation safer by eliminating the need for toxic chemotherapy before transplant. In addition, Packard Children’s is the lead site for an expanded cord blood transplant clinical trial, in which cells in the best matched cord blood are multiplied in a laboratory before being transplanted into patients, to improve the outcome of cord blood transplantation for sickle cell disease.

At the same time, doctors are researching a cure for sickle cell disease that would be readily available to all patients in the future. David Shyr, MD, and Matthew Porteus, MD, PhD, are leading research efforts to use gene therapy, specifically a technique known as CRISPR, to cure sickle cell disease. This approach involves cutting out the tiny mutation that causes sickle cell disease from a patient’s gene in the hopes that the corrected gene will then make normal hemoglobin (a protein in red blood cells) instead of sickle hemoglobin.

“Sickle cell comes from one single error in a gene. Rather than putting in a whole new gene to correct it, as with some gene therapies, which might have some unintended consequences, we are exploring erasing that one single mistake,” Dr. Shyr says.

When this gene editing approach is offered in a clinical trial starting in 2021, Packard Children’s will be the first in the world to offer it. In the meantime, Packard Children’s is also the only hospital on the West Coast participating in a different gene therapy clinical trial for sickle cell disease, run by Vertex, a pharmaceutical company.

“Gene therapy would be the ultimate cure for sickle cell disease,” Dr. Shyr says. “I am extremely hopeful that in my lifetime it will be a curable disease at birth. It’s really exciting to think that future children will never have to experience what it’s like to have sickle cell.”