FK506 (Tacrolimus) in Pulmonary Arterial Hypertension
Status:
Completed
Trial end date:
2014-08-01
Target enrollment:
Participant gender:
Summary
Mutations in bone morphogenetic protein receptor 2 (BMPR2) are present in >80% of familial
and ~20% of sporadic pulmonary arterial hypertension (PAH) patients. Furthermore
dysfunctional BMP signaling is a general feature of pulmonary hypertension even in
non-familial PAH.
We therefore hypothesized that increasing BMP signaling might prevent and reverse the
disease. We screened > 3500 FDA approved drugs for their propensity to increase BMP signaling
and found FK506 (Tacrolimus) to be a strong activator of BMP signaling. Tacrolimus restored
normal function of pulmonary artery endothelial cells, prevented and reversed experimental
PAH in mice and rats.
Given that Tacrolimus is already FDA approved with a known side-effect profile, it is an
ideal candidate drug to use in patients with pulmonary arterial hypertension.
The aims of our trial are:
1. Establish the Safety of FK506 in patients with PAH.
2. Evaluate the Efficacy of FK506 in PAH
3. Identify ideal candidates for future FK506 phase III clinical trial.