Treating CANDLE Syndrome

ISAAC: My name is Isaac Riley Barchus and I am 13 years old from Omaha, Nebraska. I love playing hockey with my friends and watching sports. KATHE: Hi, I am Kathe Barchus and I’m Isaac’s mom. We first started coming to the clinical center when Isaac was about 19/20 months old, and he didn’t get diagnosed with CANDLE until he was closer to 7. And when he was about that age, they kind of started finding the the causes of this disease and what that meant for us. DR. GOLDBACH-MANSKY: CANDLE is caused by loss of function mutations in genes that encode proteasome components, which assemble recycling units for proteins that are marked for degradation. Patients present with fevers, rashes, inflammation in the fat as well as muscles, and chronic pain. KATHE: Within two weeks after he was born, he started showing symptoms of this disease. It started really with swelling and rashes, and within 3 months, he started having fevers.
DR. GOLDBACH-MANSKY: We have successfully used strategies that block cytokine signaling for other autoinflammatory diseases. However, patients with CANDLE did not respond to these treatments. We therefore hypothesized that treatment with agents that target interferon signalling may lead to amelioration of the disease. KATHE: In 2011, he was failing pretty rapidly. We had kind of exhausted all the options that were available for him at the time, and so we were looking at a transplant. So we had actually come in for that and just kind of at the last minute they were able to talk to us about this JAGA that became available. DR. GOLDBACH-MANSKY: Drugs that block interferon signaling had not been approved by the Food and Drug Administration. We were lucky to obtain baricitinib, a JAK-1/JAK-2 inhibitor that in the lab had interferon clocking capacities, as treatment for these young children. Baricitinib, at that time, was in clinical trials for rheumatoid arthritis. DR. MONTEALEGRE SANCHEZ: In the expanded access program we enrolled 18 patients: 10 patients with
CANDLE, 4 patients with SAVI, and 4 patients with other interferon-mediated diseases. When we started to treat our patients with the JAK-1/JAK-2 inhibitor baricitinib, patients reported to feel better pretty quickly. All the chronic symptoms–the recurrent fevers, the painful rashes, the musculoskeletal pain–improved. 50% of our patients were able to achieve clinical and inflammatory remission criteria. DR. GOLDBACH-MANKSY: Having seen the the suffering of the children with rounds and rounds of ineffective treatments, to see some of the changes on treatment have been very rewarding. ISAAC: I have grown hair. That was pretty cool because, back then, I didn’t have any hair. I guess overall, I’ve been getting better. Like all my symptoms have been better as of 2011 when they weren’t at all. DR. GOLDBACH-MANKSY: His positive spirit and attitude despite of the pain that he has been experiencing through these many years has been Very encouraging to us and has been also a source for fighting to find better options for treatment. DR. MONTEALEGRE SANCHEZ: Isaac has been inspirational and his family as well. I have learned a lot about these diseases through him, but I have also learned how important it is to continue to provide better care and better treatment for these patients.