Pediatric Gene Therapy Reduces Symptoms of Rare Vascular Disease

When Ellayna Gallis was born, and in the years that followed, it was difficult to confirm a diagnosis that that was related to her rare group of symptoms: enlarged leg, abnormal foot, and vascular (involving the blood vessels) malformations.  

It wasn’t until Ellayna was 13 years old that Cleveland Clinic pediatric dermatologist Joan Tamburro, DO, along with a colleague, suspected she’d been misdiagnosed and recommended genetic testing that would reveal her true diagnosis.  

Ellayna has PIK3CA-Related Overgrowth Spectrum or PROS, the name for a group of conditions (abnormal growth, vascular conditions, and lymphatic conditions) caused by a mutation in the PIK3CA gene. The term mutation means the gene isn’t working correctly.

While there are a variety of conditions that fall under PROS, Ellayna has CLOVES syndrome (Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevis, Spinal/Skeletal Anomalies/Scoliosis), a very rare congenital disorder characterized by a combination of vascular, skin, spinal, and bone or joint abnormalities.

“Ellayna has taken anticoagulant medication to prevent or treat blood clots since she was three years old,” says Ellayna’s mother, Becky Gallis. “She has been hospitalized over the years, once due to fluid that collected around her knee; another time for cellulitis, a bacterial infection that is a common occurrence in CLOVES patients; and more recently for internal bleeding of an unknown etiology that collapsed her lung.”

Four years ago, Ellayna met Michael Kelly, MD, a pediatric hematologist-oncologist who treats patients in the Vascular Anomalies Program at Cleveland Clinic Children’s.  The Program includes specialists from several departments: dermatology, radiology, reconstructive surgery, genetics, pathology, hematology, oncology, ophthalmology and orthopaedics.  Working together, these multidisciplinary specialists diagnose and treat vascular abnormalities.

“I identified Ellayna’s major issues being overgrowth, including a very large leg and fatty overgrowth in other areas of her body, and the potential for recurrent blood clots, some of which could be life threatening,” says Dr. Kelly. “I began talking to Ellayna and her mom about systemic therapy, specifically, an oral medication that might help with these concerns.”  

Dr. Kelly explains that the overgrowth and vascular malformation is driven by changes in the PIK3CA gene that turn it on but won’t allow it to be turned off.

“These genetic changes are virtually identical to what we find in some pediatric and adult cancers. This understanding has allowed us to work on repurposing medications developed to treat cancer for use in patients with vascular abnormalities,” says Dr. Kelly.

An oral medication, VIJOICE® (apelisib), is the first and only therapy approved to treat the cause of PROS in children and adults.

Dr. Kelly’s hope was that the medication – taken orally once a day – would help improve Ellayna’s quality of life by shrinking the overgrowth and reducing the likelihood or incidence of blood clots that could lead to hospitalizations.

Following lab tests and other baselines like an EKG, Ellayna began taking a low dose of the medication about two years ago. Once it was clear she was able to tolerate that, the dosage was bumped up, followed by more testing including blood glucose monitoring. When there were no serious side effects, the daily dosage was increased a third time.

“We started out having weekly appointments, then monthly. Now we see Dr. Kelly every three months, sometimes virtually,” says Mrs. Gallis. “While Ellayna has experienced some side effects, including hair loss, we’re beginning to see changes in the size of her larger leg. It’s noticeable when she is putting on her clothing, and a pant leg doesn’t fit quite as tight as it did before.”

Now 20 years old, Ellayna has been on the current dosage for about six months, which is about when other patients using the same medication have begun to start seeing changes.

“We’re in contact with other families who are using the same medication, and while it’s not as impactful for all of them, there is still something to hope for, just as we are hopeful that with continued use of the medication, things will get better, allowing Ellayna – who eats, sleeps and breathes horses – to become even more active,” says Mrs. Gallis.