In the juveniles’ fourth month, researchers met with the Food and Drug Administration to discuss regulatory approval for clinical trials. This is the exam where KJ will be the only participant. They also worked with the Institutional Review Board (IRB) of Children’s Hospital of Philadelphia to examine clinical protocols, safety and ethical aspects of treatment. The researchers described the unprecedented speed of monitoring procedures as “through alternative procedures.”
At 5 months, they began toxicological testing on mice. In mice, experimental therapy corrected the KJ mutations and base pair errors were replaced by the correct GC pairs of animal cells. The initial dose provided a liver correction rate of 42% in the animals. At the start of KJ’s sixth month, researchers provided safety test results in monkeys. Customized basic editing therapies fed as mRNA via lipid nanoparticles did not cause toxic effects in monkeys.
A batch of clinical grades of treatment has been prepared. At 7 months, further testing of treatments was found to be an acceptable low level of non-target genetic changes. The researchers submitted FDA documents for approval of KJ’s “new drugs under investigation” or IND. The FDA approved it in a week. The researchers then began KJ with immunosuppressive therapy, preventing his immune system from responding to gene editing therapy. Then, when KJ was only six months old, he got his first low dose of custom gene editing therapy.
“Change”
After treatment, he was able to start eating more protein, but otherwise his ammonia levels would have skyrocketed. However, he was unable to separate from the drug treatments used to keep ammonia levels lowered (nitrogen remover). With no safety concerns seen after the initial dose, KJ has since received two more gene therapies, and now has a decrease in nitrogen removal drugs. He moved from 9 because there was more protein in his dietth Weight Percentile 35th Or 40th Percentile. He is currently about nine and a half months and his doctors are preparing to allow him to return home from the hospital for the first time. He needs close monitoring and may still require a liver transplant at some point, but his family and doctors are celebrating the improvements he has made so far.
