PAPPA is a protease that releases insulin-like growth factor 1 and is overexpressed in polycystic kidneys. Researchers generated fully human antibodies that block PAPPA's cleavage of IGF binding proteins 2, 4 and 5 and tested them in cell systems and in two mouse models of polycystic kidney disease: male jck mice with advanced disease and male and female Pkd1 RC/RC mice with early disease, over several weeks to months.
The antibodies blocked the cleavage in cells, and at all doses tested in male mice gave strong target engagement and reduced cystic disease, inflammation and fibrosis, with less signalling through the IGF1 receptor. In female Pkd1 RC/RC mice the protection was weaker than in males. The antibodies compared favourably with an earlier mouse antibody.
This is preclinical work. Results in mice often do not translate to humans, long-term safety has not been examined, and the authors flag sex differences in response as something to plan for in trials. Nothing here changes how patients are treated.
- Do not expect PAPPA antibodies in clinical use; no human data exist.
- Continue standard care for polycystic kidney disease, including blood pressure control and specialist review.
- Watch for early-phase human trials, which will need to look at long-term safety and sex differences.
- Counsel families that research is active but not yet a treatment.
Why it matters
It points to a new way to slow cyst growth, which matters because few treatments exist for the commonest inherited kidney disease.
Don't overread it
A mouse study; it shows nothing yet about effectiveness or safety in people.
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