Khymir’s Story: Gene Therapy to Treat Cerebral Adrenoleukodystrophy

When he was just days old, Khymir was found to be at risk for adrenoleukodystrophy (ALD) through Pennsylvania’s newborn screening. The newborn screening is a series of special tests that check a baby for health conditions at birth.

ALD is a rare genetic condition caused by mutations in the gene that prevents the body from breaking down very-long-chain fatty acids (VLCFAs). As a result, VLCFAs build up in the brain, nervous system, and adrenal glands, and destroy the protective myelin sheath around the brain’s nerve cells. This results in rapid loss of neurological function. Khymir loves superheroes, the Philadelphia Eagles, dancing and school.

There are two different forms of ALD that affect children: adrenal and cerebral. The cerebral form, known as cerebral adrenoleukodystrophy (CALD), is the most devastating form of the disease. It predominately affects boys.

Symptoms of CALD usually begin around ages 4 to 8. They include behavioral or learning deficits, deterioration in handwriting skills, poor school performance, difficulty understanding speech, difficulty reading and clumsiness. Symptoms then progress to visual disturbances, seizures, and trouble moving or speaking.

The rate of disease progression can be rapid, with total disability occurring within six months to two years. Often, if a child has symptoms of CALD, it is too late; the only option is supportive care.

Monitoring to Detect Signs of CALD

Adrenoleukodystrophy was added to the Pennsylvania newborn screening program in 2017, the year before Khymir was born. Early diagnosis through the newborn screening is helpful in identifying children at risk for ALD, but it can't predict which form of the condition — adrenal or cerebral — a child will have, or when the symptoms will start to impact them, if at all.

Every child identified with ALD through the newborn screening must receive standardized neurologic monitoring throughout childhood that includes blood work and brain MRIs. This allows clinicians to visualize the condition before a child shows any physical symptoms. If the care team sees anything concerning, they can provide personalized intervention immediately to get ahead of the condition’s rapid onset. Targeted treatment of CALD has the best outcome when performed on an asymptomatic individual.

Khymir had regular appointments with Laura Adang, MD, PhD, MSTR, a CHOP Attending Neurologist who specializes in the care of children with leukodystrophies. In April 2023, during a regular follow-up appointment, Dr. Adang discovered changes in Khymir’s brain that confirmed he has the cerebral form of the condition (CALD).

Historically, hematopoietic stem cell transplantation (also called a bone marrow transplant) was the only targeted treatment option available to prevent the progression of CALD. However, stem cell transplantation requires a match in the bone marrow registry. For Khymir and many other children, a good donor match doesn’t exist.

Fortunately, a gene therapy recently approved by the U.S. Food and Drug Administration (FDA) offers an alternative treatment. Elivaldogene autotemcel (brand name: Skysona®) is a one-time, ex vivo gene therapy that slows the progression of neurologic dysfunction. It uses a child’s own stem cells, so it doesn’t require a match in the registry.

CHOP is one of the few centers able to offer this CALD treatment option.

First CHOP Patient to Get Gene Therapy for CALD

In September 2023, 4-year-old Khymir became the first patient at CHOP to receive gene therapy for CALD. He spent about a month in the hospital. For the treatment, his stem cells were taken out of his body, treated with the healthy gene he needed, and then reinfused back into his body.  

He is now back home with his family in Folcroft, Pa. He will continue to be monitored for the rest of his life through blood work and MRIs.

"We hope it stops the progress and he can continue living his childhood,” says his mom, Tanisha, who describes her son as funny, energetic, kind, talkative and very outgoing.

“He loves superheroes, loves the Eagles, Sixers and Phillies, likes dancing, and loves school,” she says. "We are so grateful for all the doctors and nurses who helped us, especially Dr. Adang. She's been really great with us and supporting us.”

Dr. Adang is hopeful that halting CALD before its effects take hold will put Khymir and other kids like him on a path to a normal life.

“This is a condition where huge gains have been made,” says Dr. Adang. “Newborn screening, standardized monitoring programs, and gene therapy are going to save lives. Our monitoring tells us there is growing risk before a child has permanent injury. The MRI changes well before the child changes, so it’s a really good screening tool. As long as you can find children pre-symptomatically, gene therapy has the potential to be transformative, and our children can live long, healthy lives.”

Learn more about CHOP’s innovation in cell and gene therapies.