Teamwork Behind the Scenes Fuels Major Medical Breakthroughs

The Center for Clinical and Translational Science and Training (CCTST) provided the investigational backbone that led to the FDA approval of two drugs for rare diseases that have eluded researchers for many years.

The CCTST, based at Cincinnati Children’s and led by director James Heubi, MD, serves the University of Cincinnati and its Academic Health Center partners. Its two most significant accomplishments culminated within a three-month span early in 2015.

An arduous 25-year process led to the March 17 FDA approval of Cholbam (cholic acid) for treatment of bile acid synthesis disorders due to single enzyme defects, conditions estimated to occur once in every 80,000 births.

Spearheaded by Heubi and Kenneth Setchell, PhD, director of the Clinical Mass Spectrometry Lab at Cincinnati Children’s, clinical trials to establish the safety and efficacy of cholic acid therapy were based exclusively in the CCTST’s Clinical Translational Research Center (CTRC).

As a result of this investigator-initiated “bench to bedside” drug development - from conceptualization to approval - a daily pill has replaced liver transplant as treatment for these conditions.

Three months later, more major news arrived for the CCTST. Lymphangioleiomyomatosis (LAM) is a rare and frequently fatal lung disease of women, affecting only five people per million. It is characterized by smooth muscle infiltration and cystic destruction of the pulmonary parenchyma. The safety and efficacy of sirolimus (Rapamune) in the treatment of LAM was established by the multi-site MILES study, led by UC’s Frank McCormack, MD.

Locally, the trial was based in the CTRC, in collaboration with the Rare Lung Disease Consortium led by Bruce Trapnell, MD, MS, of the Division of Pulmonary Medicine. FDA approval was announced on May 28.