Pappalysin 2 (PAPP-A2) Enzyme Replacement
| Status: | Completed |
|---|---|
| Conditions: | Endocrine |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 7/11/2015 |
| Start Date: | April 2015 |
| End Date: | March 2016 |
| Contact: | Andrew Dauber, MD |
| Email: | Andrew.Dauber@cchmc.org |
| Phone: | 513-803-7027 |
PAPP-A2 Enzyme Replacement Therapy Using Plasma Transfusion
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.
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.
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.
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.
Inclusion Criteria:
- Homozygous for a defect in PAPPA2.
Exclusion Criteria: None
We found this trial at
1
site
3333 Burnet Avenue # Mlc3008
Cincinnati, Ohio 45229
Cincinnati, Ohio 45229
1-513-636-4200
Cincinnati Children's Hospital Medical Center Patients and families from across the region and around the...
Click here to add this to my saved trials
