Pui Lee, MD, PhD, discusses the ultimate results of his study, “mTORC1 connects the spectrum of pathology in experimental models of Still’s disease and macrophage activation syndrome,” the clinical significance of these results, and the next steps for his team. Lee is a pediatric rheumatologist at Boston Children’s Hospital.
Investigators determined that the mTOR Complex 1 (mTORC1) pathway was very active in both animal models and human transcriptomic data by assessing the expression of different genes in the blood from a variety of studies, including finding human samples with this condition and concluding that this pathway was also activated in those samples.
“[The clinical significance] is that we may have a lead for another class of medications that may be effective for this condition, particularly for mTOR inhibitors, which directly targets the pathway we're discussing here,” Lee explained. “[Although] some of these drugs are already clinically available… to treat other indications… I think this could be additional option for kids that don't respond well, to develop biologics.”
Lee and his team strive to learn more about whether this is a feasible approach for this patient population. He noted that there was 1 case report from Chili that showed that an mTORC inhibitor worked well in a patient who was previously refractory to the currently available medications.
“Pediatric rheumatology is a fairly small field that may not be familiar to many people,” Lee concluded. “It's an evolving field where we have lots of limitations in terms of getting new drugs approved and doing clinical trials in children. This is an area that deserves more attention in general, not specifically to our study, but this is an area where I think a lot there's a lot more research needed for these kids. We often neglect them in a world where a lot of people don't think kids can develop these very severe conditions.”
Huang Z, You X, Chen L, et al. mTORC1 links pathology in experimental models of Still's disease and macrophage activation syndrome. Nat Commun. 2022;13(1):6915. Published 2022 Nov 28. doi:10.1038/s41467-022-34480-6