Tissue distribution of ³⁵S-metabolically labeled neublastin (BG00010) in rats

Neublastin (NBN) is a neurotrophic growth factor that promotes the survival and regenerative properties of nociceptive neurons and has been tested in clinical trials as a treatment for neuropathic pain in individuals with sciatica and painful lumbosacral radiculopathy. Like many low molecular weight heparin binding proteins, NBN is rapidly cleared from the blood following systemic administration. To explore ADME properties of NBN in rats, we used metabolically ³⁵S-labeled NBN following IV and SC administration quantifying counts and intact protein in kidney, liver, brain, serum, and urine at 5 min, 8 h, 24 h and 48 h, and biodistribution in whole body carcasses by QWBA at 2, 8, 48, 96, and 168 h post dose. NBN is rapidly taken up by tissues mainly by liver and kidney and then degraded. Products of degradation are excreted in urine or recycled and utilized for resynthesis. The data we generated for NBN provides a first look at the complex clearance mechanisms for this protein and should aid in the design of ADME studies for other heparin binding proteins.