Her whole life, 19-year-old Ashlynn Malone has struggled with fatigue, outbreaks of severe pain, and hospitalizations due to sickle cell disease (SCD). 

That’s why Ashlynn jumped at the chance to join a clinical trial designed to stop her SCD symptoms by modifying her blood stem cell genes. Ashlynn has early access to the treatment at Cook Children’s Medical Center – Fort Worth, the RUBY Trial’s only pediatric site in Texas.  

The RUBY Trial uses an experimental technology called EDIT-301 for editing genes. Cook Children’s hematologist Clarissa Johnson, M.D. said preliminary results show the EDIT-301 treatment provides long-lasting relief from the painful flare-ups and anemia that patients like Ashlynn experience when their blood flow is blocked by sickle-shaped red blood cells. 

“This is a more potent treatment than what we have been able to offer thus far,” said Dr. Johnson, who heads up the Sickle Cell Program at Cook Children’s, which serves about 400 patients. “It’s not a cure, but a transformative treatment.”

The first RUBY Trial transplant at Cook Children’s was done in January 2024. Ashlynn will be the second. Cook Children’s is now working to enroll qualified patients ages 12-17 because the enrollment for adults has closed.

“The trial was always planned to include adolescents,” Dr. Johnson said. “We were chosen because I pursued this for our patients, and we were able to demonstrate to the company that we had the expertise and resources to conduct this trial with great support from our research department.”

How does EDIT-301 work? Through technology that edits the genes involved in SCD to make them able to produce healthier blood cells. The RUBY Trial is a study that measures the safety and effectiveness of that treatment.

Gretchen Eames, M.D., serves as Medical Director of the Stem Cell Transplant Program at Cook Children’s. Dr. Eames said the program has an extensive track record since 1985 of providing leading-edge therapies and caring for patients with SCD. 

“Our outcomes as well as our superb and experienced research team are the reasons we have been chosen to participate in clinical trials such as the RUBY Trial,” she said. “We jumped at the chance to bring this transformative therapy to the patients of North Texas and beyond.”

Previously, the only definitive therapy for SCD was undergoing a stem cell transplant from a family member -- a much more intensive therapy, with greater risks. EDIT-301 eliminates the need for a matched donor since it uses the patient’s own cells.

“Now we have a gene therapy that can give hope to those patients who do not have a family bone marrow donor or who are ineligible to receive a traditional bone marrow transplant,” Dr. Eames said.

Ashlynn met the criteria to enroll in the RUBY Trial in 2023. Her stem cells were collected at Cook Children’s and shipped to the manufacturer’s lab. After about 12 weeks, the edited genes will be shipped back to Fort Worth and infused into Ashlynn’s blood. Then she’ll go through follow-up testing for at least two years.

She has confidence in her doctors -- and she’s hopeful that the treatment will end her SCD pain and exhaustion. Ashlynn knows she’ll need some chemotherapy before the infusion, and there are potential side effects, but she says the risks are worth the expected outcome.

“I can’t wait to be done with sickle cell,” she said. “I’m more excited than anything.”

Here’s a closer look at the potential for this treatment to expand the genetic therapy options for people living with severe SCD.

Three Treatment Phases

An estimated 100,000 people in the U.S. have sickle cell disease, an inherited disorder most common in people of African descent. A mutation in the patient’s genes causes the hemoglobin proteins – the body’s oxygen transporters -- to bend so that the red blood cells curve like crescent moons instead of round discs. Instead of flowing smoothly through the blood vessels, the sickle-shaped cells get clumped up. It causes pain and can lead to anemia, organ damage or stroke.  

Dr. Johnson said the EDIT-301 treatment targets the genes that makes fetal hemoglobin. Adults with healthy hemoglobin don’t usually need fetal hemoglobin. The treatment tweaks the genes so that they start producing very high levels of fetal hemoglobin to counteract effects of the sickled hemoglobin.  

The clinical trial spans about 2½ years and consists of three parts:

1. Phase One: Selected candidates are injected with a medication that moves their blood stem cells out of the bone marrow. An intravenous line collects the stem cells, which are sent to the Editas Medicine laboratory, where genes from those cells are edited via CRISPR technology.
2. Phase Two: After the cells are edited and shipped back to the trial site, the patient receives four days of chemotherapy to wipe out any remaining stem cells in their bone marrow. “Think of it like a garden,” Dr. Johnson said. “You have to clear out the garden to make room to plant something new.” Cells with the edited genes are transplanted into the body and travel to the bone marrow. The patient remains hospitalized until they can consistently create white blood cells to reduce risk of infection and are not needing frequent transfusions of red blood cells and platelets.
3. Phase Three: Follow-up tests check for any side effects and measure the impact of the treatment on the patient’s blood quality, heart and lungs.  

Results are encouraging from other sites nationally where the clinical trial started earlier, according to Dr. Johnson and Dr. Eames. The edited cells have increased the production of fetal hemoglobin in most participants in the study, leading to fewer SCD complication and improved quality of life.

Departments across Cook Children’s play a role in the RUBY Trial. The effort includes the research, apheresis, radiology, lab, pharmacy and hematology departments, along with the stem cell transplant physician and team. 

Ashlynn’s Perspective

Ashlynn was born with SCD because both of her parents carried the genetic trait. One cousin also has the disorder, but no one else in her family.  She’s a patient of hematology/oncology physician Timothy McCavit, M.D., who directs the Bleeding Disorder Program and Hemophilia Treatment Center at Cook Children's.

“I was never really able to do things other children were able to do because I had physical limitations,” she said. “When I was younger, I was prone to getting sinus infections because my immune system wasn’t as strong. If I push myself too hard, that could cause me to have a pain episode. So I always had to limit myself.” 

Hard exercise, stress or allergies can bring on an SCD pain episode for Ashlynn. She described the sensation as an aching in her back, head, arm … anywhere in her body. Sometimes the pain is sharp.

To control mild pain, she takes Tylenol. She’ll take a prescribed medication for moderate pain. And if that doesn’t work within a day or two, she goes to the Emergency Department. She estimates she’s been 50-100 times to different hospitals, including Cook Children’s Medical Center – Prosper, a short drive from her home in Little Elm.

“I have a natural high pain tolerance. If it gets to a point where I feel like I’m going to start crying, that’s when I know it’s getting bad,” Ashlynn said.

She first heard about the RUBY Trial during one of her hospitalizations last year, when Dr. Johnson brought it to her and her mom’s attention. Ashlynn was eligible because the medications she was taking for SCD didn’t stop her frequent pain episodes.

Optimistic that the clinical trial would help, she was screened and accepted. Her stem cells were collected in January 2024, placed in an ice chest, and shipped to the Editas Medicine lab.   

She has received regular transfusions of donated blood while waiting for her edited genes to be shipped back, likely by April. Ashlynn looks forward feeling well enough to reach her goals: Travel to Japan, start working out, and own a business. She’d like to spread awareness of SCD.

“If you know someone who has sickle cell disease, just know there are going to be some days when they’re not really going to want to hang out or do much physical activity,” she said. “Just be more understanding about it.”

Bringing Hope

SCD can complicate school, work, travel and other plans because a pain episode can happen at any time. That’s why a treatment like EDIT-301 gives hope to patients and families dealing with the interruptions and stress that chronic illnesses cause.

“Having a chronic illness is very consuming, not just for the child who's affected, but also for the family,” Dr. Johnson said.

Many parents tell her they’re excited about genetic therapy because of the prospect of making long-term plans without worrying about their child’s SCD flaring up on a trip, for instance. Some families, however, are more hesitant. 

“It's a big decision,” she said. “We know that not everybody's going to necessarily be first in line. But I think the longer we see this out there and see the difference it makes for people, that will be what encourages others to give it a try.”

After the RUBY Trial ends, the manufacturer may choose to submit the data to the U.S. Food and Drug Administration for approval of the treatment. 

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The people who are already predisposed to developing the disease not only have a greater risk of developing cancer but also passing those genes on to their children.

Because of the advances in genetic testing and the importance of detection of those inherited cancer predispositions, Cook Children’s has started the Genetic-Oncology Clinic.

“We are trying to educate families and patients to increase awareness,” said Kelly Vallance, M.D., MPH. “But also to catch the cancer early, know the warning signs and find the way we are able to intervene and give these kids the normal lives they deserve. We do that by catching it early and teaching them what to look for.”

The Genetic-Oncology Clinic provides care and counseling to children and their families with a predisposition to cancer. The program, one of only a few in the country, is a collaboration among pediatric oncologists, geneticists and genetic counselors who provide education, guidance, therapy and routine cancer surveillance studies when indicated for children with a predisposition to cancer.

Patients range from newborns to adults through the Life After Cancer Program at Cook Children's.

"Research coming out now recommends that almost all pediatric solid tumor patients, as well as certain leukemia patients, have genetic testing done to see if they are at increased risk for developing secondary malignancies," said Heather Jernigan, a hematology and oncology clinic nurse and the nurse coordinator of Genetic-Oncology Clinic since it started a year and a half ago. "We know that almost every patient who gets cancer treatment is at risk for developing secondary malignancies. What we are learning is that with some patients with genetic predisposition syndrome that risk increases."

Becky Althaus was a catalyst to making the clinic a reality. Althaus worked with Mary Kukolich, M.D., medical director of Genetics, 40 years ago. The two of them worked together for about 19 years and Althaus said that’s where she was taught about genetics. She already owned a masters in nursing, and then became certified as a genetics counselor, earned her Ph.D. in genetics and a nurse practitioner. She went on to help start genetic-oncology programs in three different locations before coming full circle by joining Cook Children’s and working with Dr. Kukolich again.

“Between 10 to 14 percent of all pediatric cancers have a genetic component, so that means they have a genetic predisposition,” Althaus said. “Because of that we really need to be testing most children who are diagnosed with cancer.”

Genes are passed from parents to offspring and specify traits. Humans have approximately 20,000 genes. A mutation is a change in the DNA sequence that can occur in one of two types of genes:

• Somatic mutations occur in body and cells and are not passed on. They weren’t born with a predisposition.
• Germ line mutations occur in the eggs and sperm and can be passed on to offspring. This is a hereditary gene, meaning the child was born at risk for cancer at the moment of conception.

The Genetic-Oncology Clinic sees patients who are at risk for having cancer passed on to them genetically. That can mean their siblings or other family members could be at risk for developing the same cancer, or that the patients may eventually pass the gene on to their own children.

“A lot of times hearing the information for the first time is very difficult, surprising and causes a lot of fears for families, parents and patients,” Dr. Vallance said. “Especially our older cancer survivors who are being tested. To learn that they may be at risk for a second cancer and they may be at risk for passing along a gene that may predispose their children to developing cancer. At first it’s a lot of information to process. Over time everyone has been appreciative of knowing. I’ve not found anyone who says they wish they didn’t know. It gives them almost a sense of power that they know what to look for. They can educate themselves further. They can think seriously about not smoking, or eating healthier or taking better care of themselves. It empowers the families a little bit. It allows us to initiate early screenings and help them.”

Patients with predisposed cancers such as melanoma and leukemia are seen in the clinic. The clinic also allows for other specialties to be brought in during a patient's visit. For example, gastroenterology doctors and surgeons are brought in to help FAP (familial adenomatous polyposis) patients because they are at such and increased rate to develop colon cancer early in life before the age of 40.

The FAP patients are recommended to begin colonoscopies from ages 10 to 15, depending on symptoms. Jernigan works very closely with the GI staff through the clinic to schedule the patient's procedures.

“Certainly the care we provide each patient kind of expands to care for the whole family,” Vallance said. “A lot of our patients come to us because they’ve just been diagnosed with cancer. We’ve had many patients that may have just lost a parent to kidney cancer or colon cancer or multiple family members and now they find out they have this gene. Through our clinic we really want to be able to support the child and the family, provide social service support as needed and clinical therapy as we can. We can coordinate with the GI specialists and the surgeons and get these families the full care they need. I’m proud of our group that we really work hard together to make sure that anyone that may be affected in the family can get the support and the services they need too.”

Althaus says her heart breaks when she has to tell parents that their child has cancer, but she says the testing involved in the clinic can also bring comfort too.

For example, a parent dies at a young age from melanoma. A child can be tested to see if he or she is predisposed to the gene because of the high risk factor of developing the same cancer.

“That’s something the child might not have known about if we hadn’t done this testing,” Althaus said. “Now the child is getting closer surveillance from our staff for melanoma and pancreatic cancer in the future and if it’s detected, it is more likely to be in a treatable stage. This is truly life-saving work – genetic testing and counseling. It’s exciting to be a part of this. The impact can be for 50 or 70 years because we are seeing many of these patients at such an early age. If we can prevent cancer that has to be our ultimate goal for existence. It’s just so rewarding to think we might be able to prevent cancer or we might be able to detect cancer early for which a child is predisposed and save a life.”

Currently, the clinic is once a month and the genetics-oncology team sees about 20 patients a day. If a child does have a genetic form of cancer, other family members will then be looked at right away.

"I'm a nurse, but I'm a mom too and if the roles were reversed and somebody told me, 'Hey there's a chance your child might develop cancer I would want to know everything there is to know and I would want to make sure there's someone knowledgeable I could contact," Jernigan said. "I think our families trust us and that's why they are in treatment or surveillance. They trust the information we are giving them. It is the most up to date information we have. We are providing family-centered care. We are going to give that family our undivided attention while they are at the clinic. That says a lot about what we are able to offer kids and families at Cook Children's. I think it's important that we continue to do that for families in every way possible."

One way that Jernigan says the clinic could help patients is answering a simple question for parents whose child has cancer: Why?

"That's one of the amazing things that Becky brought to us that Dr. Vallance and I didn't even know about," Jernigan said. "If we are able to say, 'You know what? You have a genetic predisposition syndrome that was probably going to happen no matter what. Number one, we are able to give those families a reason for why their child developed cancer, but we are also able to test the rest of the family. That can give everyone peace of mind."

Althaus said those answers are what makes the clinic rewarding.

“It’s so rewarding to be able to give the parents the why and how it happened to begin with,” Althaus said. “That is such a basic need for families when they have a difficult diagnosis and we are able to either prevent a new cancer or detect a new cancer very early that might have been life threatening for that child. If we know ahead of time and we are looking for it, we can catch it when it’s just a tiny cancer and when treatment is so much more effective. This means the chance for a cure is so much greater.”

Count your many blessings. See what God has done!"

- Johnson Oatman Jr.

I grew up knowing every word to the song, “Count Your Many Blessings,” but never truly appreciated the powerful message until this past summer.

Our daughter, Eliza, got sick June 19, 2015. It seemed like a typical stomach bug. But by the next day, we knew something was wrong. She was hospitalized at Lakeside Covenant in Lubbock, Texas a couple days later.

It was there that we received her diagnosis, Hemolytic Uremic Syndrome, or HUS, caused by E coli. They arranged for us to be immediately flown to Cook Children’s Medical Center in Fort Worth.

Three letters: H.U.S – that would change our lives forever.

Eliza’s kidneys began shutting down; she was exhibiting signs of neurological disturbances as well. We couldn’t believe our healthy child was going downhill so quickly. She was transferred to the PICU (Pediatric Intensive Care Unit), where we would spend the next 26 days.

The staff in the PICU started Eliza on dialysis right away. As a mother, it was my worst nightmare, to see my child unresponsive, lying on a bed with multiple machines keeping her alive.

Eliza wasn’t following the normal progression of HUS. She began having seizures, her kidneys still refused to work, she continued to have gastrointestinal bleeding, and was showing signs of extreme pain.

By this point, she had gone through several blood transfusions, plasma exchanges, dialysis around the clock, numerous MRIs, CAT scans, EEGs, and EKGs. She had a whole team of doctors and they were all stumped. We were constantly told that she wasn’t their typical HUS patient.

Thankfully, Eliza’s nephrologist, Dr. Jennifer Willis, kept researching and questioning Eliza’s unusual symptoms. This would eventually save Eliza’s life. She suspected Eliza not only had HUS, caused by E coli, but also atypical HUS, a genetic disease.

She approached my husband and I about running a genetic test on Eliza to confirm the atypical HUS diagnosis, but the results would take up to 8 weeks. In the meantime, she wanted to try a medication called Soliris. She warned us that it was very expensive and she was not sure if insurance would cover it.

We continued to pray, we asked for prayers, and decided it was worth the risk. We just wanted our Eliza back! This was the first moment I truly realized we might lose our precious baby. We had been so hopeful and optimistic the entire time, but my hope was gone. I pleaded with God to be with Eliza and her medical team and save her life.

He answered my prayers and the prayers of many who were praying all over the world for her. Dr. Willis was right, after two doses of the medication, we began to see dramatic improvement. Eliza woke up, began talking, and progressed more and more every day.

Fifty days after exhibiting her initial symptoms, we were released from Cook Children’s. During Eliza’s summer at Cook Children’s we became friends with all the employees. We knew the PICU nurses, the receptionists and Eliza’s specialists.

Cook Children’s became our home. Eliza now looks, sounds, moves, and plays like a normal 2 year old. The syndrome, atypical HUS, has long-term side effects on some of her organs.

Currently, Eliza’s kidneys function at 60 percent. She is on multiple medications for both seizures and high blood pressure. The atypical HUS diagnosis was correct, as genetic tests eventually confirmed. Eliza receives a Soliris infusion every other week. Our sweet girl is a model patient. She jumps on the scale, stands to get measured, picks an arm for the blood pressure cuff, and watches while her port is accessed.

We owe so much to all the wonderful doctors, nurses and staff at Cook Children’s, as well as family, community, and the countless people praying for Eliza.

Is it a normal life? No, but it is her life and we thank God every day.

“Count your blessings, name them one by one. Count your many blessings, see what God has done.”

But the research may simply be a matter of parents being more mindful of autism than they were previously.

“What is telling is that the overall prevalence of developmental disabilities hasn’t increased,” said Joyce Mauk, M.D., CEO and medical director of the Child Study Center. “Some of this is diagnostic substitution. Many more children with language disorders and some unusual features of behavior are now being diagnosed with autism.”

Dr. Mauk, who is board certified in pediatrics and neurodevelopmental pediatrics, said examiners are more likely to diagnose children with more subtle or mild symptoms of the autism spectrum than ever before because of the attention autism has gotten in recent years.

The Centers for Disease Control and Prevention and National Center for Health Statistics stated reported that 1 in 45 children were diagnosed with autism in 2014, a leap of nearly 80 percent from 2011 to 2013 (1 in 68 children were diagnosed during that time period).

“The survey changed from 2013 to 2014 and the categories for autism were more inclusive in the most recent study,” said Lena Zettler, director of Psychology at Cook Children’s. “They included other developmental delays. The incidence isn’t necessarily changing, but awareness is.”

Both Dr. Mauk and Zettler agree that the focus should remain on the science we know.

Autism is more common if there other family members who are on the spectrum. Higher incidence in autism can occur if:

• The father is older
• Pregnancies are less than two years apart
• Preemies are at a higher risk for developmental delays (including, but not limited to the autism spectrum)

The survey found that the majority of children diagnosed were boys than girls, with a 75 to 25 ratio. Fifty-nine percent were identified as non-Hispanic White.

Another key factor that some point to is the fact that more than 67 percent of the children who were diagnosed had at least one parent with more than a high school education, which could mean they are more likely to be aware and educated of the symptoms of autism, making for quicker identification.

“There is of course a lot we still don’t know about the underlying factors that cause autism, but I think the fact that people are becoming more aware is a great start,” Zettler said. “It makes for quicker diagnosis and care for the child.”