A phase 1, single-dose study of fresolimumab, an anti-TGF-β antibody, in treatment-resistant primary focal segmental glomerulosclerosis.

Primary focal segmental glomerulosclerosis (FSGS) is a disease with poor prognosis and high unmet therapeutic need. Here, we evaluated the safety and pharmacokinetics of single-dose infusions of fresolimumab, a human monoclonal antibody that inactivates all forms of transforming growth factor-β (TGF-β), in a phase I open-label, dose-ranging study. Patients with biopsy-confirmed, treatment-resistant, primary FSGS with a minimum estimated glomerular filtration rate (eGFR) of 25  ml/min per 1.

A short carboxy-terminal domain of polycystin-1 reorganizes the microtubular network and the endoplasmic reticulum.

Mutations of PKD1 cause autosomal dominant polycystic kidney disease (ADPKD), a syndrome characterized by kidney cysts and progressive renal failure. Polycystin-1, the protein encoded by PKD1, is a large integral membrane protein with a short carboxy-terminal cytoplasmic domain that appears to initiate multiple cellular programs. We report now that this polycystin-1 domain contains a novel motif responsible for rearrangements of intermediate filaments, microtubules and the endoplasmic reticulum (ER).