PAPPA2 as a Therapeutic Modulator of IGF-I Bioavailability: in Vivo and in Vitro Evidence

Abstract

CONTEXT: presented with growth retardation, elevated total IGF-I, and IGFBP-3 but decreased free IGF-I. OBJECTIVE: To determine whether plasma transfusion or recombinant human (rh)PAPPA2 could increase free IGF-I in patients with PAPPA2 deficiency or idiopathic short stature (ISS). DESIGN: experimentation. SETTING: Academic medical center. PATIENTS: Three siblings with PAPPA2 deficiency and four patients with ISS. INTERVENTIONS: for 4 hours. Intact IGFBP-3 and free IGF-I levels were assayed via ELISA. MAIN OUTCOME MEASURES: Free IGF-I concentrations. RESULTS: studies demonstrated a dose-dependent increase in free IGF-I and decrease in intact IGFBP-3 after the addition of rhPAPPA2. The increase in free IGF-I was more pronounced in patients with PAPPA2 deficiency compared with those with ISS. CONCLUSIONS: PAPPA2 plays a key role in regulation of IGF-I bioavailability. rhPAPPA2 is a promising therapy to increase free IGF-I levels both in patients with PAPPA2 deficiency as well as in patients with ISS.