Understanding the Goals of TSC Steps and Use of Sirolimus: Darcy Krueger, MD, PhD

WATCH TIME: 5 minutes

"In tuberous sclerosis, we have such a high rate of epilepsy that occurs in people with a genetic condition. Unfortunately, all of our available treatments, particularly our medical treatments, fail to fully control seizures in nearly half of our patients. This has created a challenge for us medically, it has major impacts for long-term learning and development, and of course, quality of life and opportunities."

Tuberous sclerosis complex (TSC) is caused by a genetic mutation in TSC1 or TSC2, resulting in dysregulation of the mechanistic target of rapamycin (mTOR) signaling pathway. This rare, multi-system disease causes non-cancerous tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin. Initiated in 2020, TSC Steps, a phase 1/2 clinical trial, will look to see whether use of TAV-18 (Tavanta Therapeutics) powder, a novel formulation of sirolimus (Rapamune), can be a disease-modifying therapy for preventing or delaying seizure onset in TSC.

The study features 5 children who were between the ages of 0-6 months at the time of enrollment and have a confirmed diagnosis of TSC based on established clinical or genetic criteria. Led by Darcy Krueger, MD, PhD, the study excludes those with a prior history of seizures, have been treated in the past or currently with conventional anticonvulsant medications, systemic mTOR inhibitors, ketogenic-related special diet, or another antiseizure therapeutic agent, device, or procedure.

Sirolimus, the main formulation being assessed, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection, and treat a rare lung disease called lymphangioleiomyomatosis. To learn more about the origin of the study, including why sirolimus holds potential as a disease-modifying therapy, NeurologyLive^® sat down with Krueger. Krueger, director of the Tuberous Sclerosis Clinic at Cincinnati Children, provided insight on how the drug was previously used and the significance if it proves to delay seizure progression.