Pilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome

Hermansky-Pudlak Syndrome (HPS) is a rare autosomal recessive disease consisting of oculocutaneous albinism and a platelet storage pool defect. The most serious complication of this disorder, pulmonary fibrosis, occurs only in genetic subtypes HPS-1 and HPS-4 and is generally fatal in the fourth or fifth decade. HPS-1 is very common in northwest Puerto Rico. There is no effective treatment for the pulmonary disease of HPS (HPS-PF), which resembles idiopathic pulmonary fibrosis (IPF). A preliminary study of the antifibrotic drug, pirfenidone, gave promising results for mild to moderate HPS-PF, but not for severe pulmonary fibrosis. A second study is currently addressing only mild to moderate HPS-PF. Other drugs, studied in IPF as single agents, have some efficacy for mild to moderate disease, but none has had a major effect on mortality. Recently, a call has been made for consideration of multi-drug therapy (i.e., an oncologic approach) for severe pulmonary fibrosis. Based upon positive responses from companies producing relevant drugs, we propose a multi-drug trial using five agents: Losartan, Zileuton, a generic statin (Pravastatin), generic N-acetylcysteine, and generic Erythromycin. Participants with severe pulmonary fibrosis will be drawn largely from the Puerto Rican population. Eligibility will require a molecular diagnosis of HPS-1 or HPS-4, radiographic evidence of interstitial lung disease, persistent pulmonary function testing less than or equal to 45% of predicted after bronchodilation, and absence of other causes of lung dysfunction. Participants will be admitted to the NIH Clinical Center for a 21-day admission to establish baseline function and to begin medication therapy. Follow-up admissions (3 days) will occur every 3 months. The primary outcome parameter will be survival at 2 years.