Infant KJ Muldoon was born with carbamoyl phosphate synthetase 1 (CPS1) deficiency, a condition so rare that only about 1 in a million babies are diagnosed with it. Outcomes are often severe, including impacts on intellectual development, and only a few decades ago, close to half of children diagnosed at birth didn’t survive until age five.
There are treatments available, but nothing so far compares to what doctors hope we can see from the gene therapy treatment KJ received.
The process took 6 months from diagnosis to treatment, and so far, Muldoon is reportedly thriving.
What Is CPS1 Deficiency & Why Is It So Serious?
When we eat, our bodies undergo numerous processes to metabolize our food and turn it into usable energy. For protein, our bodies utilize an enzyme known as CPS1. Metabolizing protein creates ammonia as a byproduct, and CPS1 removes it from the blood, preventing buildups.
When these levels get too high, a person becomes hyperammonemic, which affects the brain. According to the National Urea Disorders Foundation, the relationship between ammonia and the brain isn’t fully understood, but excess ammonia can result in developmental delays, coma, or death. They note that the last study on this occurred decades ago, when treatment options were still limited, and about half of children with newborn onset did not survive to age five.
According to the NIH, treatment typically involves keeping the child on a low-protein diet and doing everything possible to hold out until he’s strong enough for a liver transplant, often performed in the first year of life.
KJ Muldoon Receives Gene Therapy
The technology used for Muldoon’s procedure has been developing for more than half a century, starting with humans’ beginning to understand DNA. According to the American Society of Gene & Cell Therapy’s timeline, studies that tested gene therapy in humans began in 1990.
Baby Muldoon’s treatment takes basic gene therapy a giant leap beyond where it began, with personalized genetic treatment. The NIH explains:
A team of researchers at the Children’s Hospital of Philadelphia (CHOP) and the Perelman School of Medicine at the University of Pennsylvania (Penn) developed the customized therapy using the gene-editing platform CRISPR. They corrected a specific gene mutation in the baby’s liver cells that led to the disorder. CRISPR is an advanced gene editing technology that enables precise changes to DNA inside living cells. This is the first known case of a personalized CRISPR-based medicine administered to a single patient and was carefully designed to target non-reproductive cells so changes would only affect the patient.
Baby Muldoon started treatment earlier this year at 6 months old, and signs of success were quickly visible.
What Signs Did His Medical Team See?
The team gradually increased Baby Muldoon’s protein intake, and they were still able to lower the dosage of medications that helped keep the ammonia levels in his blood down.
It was looking good, and then the baby got sick.
Various factors can cause a CPS1 deficiency patient’s ammonia levels to spike, and viral illnesses are perhaps the most common. When the baby came down with his first illness during treatment, the team was worried—but then he “just shrugged the illness off,” according to Kiran Musunuru, M.D., Ph.D., a geneticist working on Muldoon’s case.
By the way, according to Motherly, the total cost of this gene therapy was pretty close to the same $800k that is commonly spent to cover liver transplants and ongoing treatment. This suggests that these costs per patient could come down over time, making gene therapy a more accessible treatment than the standard transplant option.
Is The Fix Permanent?
KJ Muldoon’s health will be monitored exceptionally closely now, as the first human to receive this type of treatment, and monitoring will continue for the rest of his life, according to a release from Children’s Hospital of Philadelphia.
For now, they’re using the phrase “cautiously optimistic. ” They know there’s still a lot to learn about the long-term effects of this treatment, but they see positive signs, including his ability to tolerate increased protein intake and his weathering childhood illnesses without a serious protein spike.
The child’s first treatment was in February, and he’s continued receiving infusions, with follow-ups in March and April. His team must continue evaluating and deciding on the best options as he grows and moves forward.
For now, though, a baby whose prognosis was initially grim is now meeting the milestones his parents were waiting for, like waving and rolling over.