Pappalysin 2 (PAPP-A2) Enzyme Replacement
- Conditions
- Short Stature, Idiopathic
- Interventions
- Other: Fresh Frozen Plasma
- Registration Number
- NCT02412943
- Lead Sponsor
- Children's Hospital Medical Center, Cincinnati
- Brief Summary
This study evaluates the transfusion of fresh frozen plasma containing the enzyme PAPP-A2 into the a female adult. This female adult has a mutated version of PAPP-A2 that prevents the unbinding of IGF-1 from IGF binding proteins. The investigator's hypothesize that transfusion of plasma with donor PAPP-A2 will lead to the unbinding of IGF-1 from its binding proteins and that they will be able to measure free IGF-1 in the blood of this female adult.
- Detailed Description
PAPP-A2 is a plasma protease that is known to cleave IGFBP-3 and IGFBP-5. It is thought that this cleavage frees up IGF-1 from its bound form allowing it to become the active free IGF-1. The participant has short stature accompanied with elevated plasma levels of both IGF-1 and IGF binding protein 3 (IGFBP-3). Genetic analysis of the participant identified a novel missense mutation in PAPPA2 (Ala1033Val). This gene is a perfect candidate to explain our patients' phenotype. The investigators' hypothesis is that loss of activity of PAPP-A2 leads to an inability to cleave the IGF binding proteins and thus an overall elevation in IGFBP-3 and consequent elevation in total IGF-1. However, this IGF-1 cannot be freed up and is thus not able to be active leading to short stature. The patient's missense variant is predicted to be damaging by in silicon prediction models such as Polyphen2. Furthermore, two knock out mouse models of PAPPA2 as well as a zebrafish knock out exist, all showing growth retardation (post-natally in the mice). Taken together, this is definitive evidence that the patients' mutation in PAPPA2 is responsible for their short stature phenotype.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 1
- Homozygous for a defect in PAPPA2.
None
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description PAPP-A2 Enzyme Replacement Fresh Frozen Plasma A 20 cc/kg transfusion of Fresh Frozen Plasma will be given over 3 hours on day 0.
- Primary Outcome Measures
Name Time Method Decrease in IGF-1 5 minutes Decrease in either total IGF-1 or IGFBP-3 of 20% or greater as a clinically meaningful decrease in levels
- Secondary Outcome Measures
Name Time Method Length of decrease in IGF-1 up to 30 days
Trial Locations
- Locations (1)
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States