Kenneth P. Karey

TL;DR: The first successful demonstration of the integration of a perfusion bioreactor and a four‐column periodic counter‐current chromatography system for the continuous capture of candidate protein therapeutics is reported, demonstrating the potential of integrated continuous bioprocessing as a universal platform for the manufacture of various kinds of therapeutic proteins.

TL;DR: Results indicate that purified rhASM can be activated in vitro by loss of the free thiol on the C-terminal cysteine via chemical modification, dimerization, or deletion of this amino acid residue.

TL;DR: This method provides an effective process for generating recombinant cell lines producing high levels of therapeutic proteins, with the benefits of rapid and accurate 96‐well plate clone screening and elimination of unstable clones at an earlier stage in the development process.

TL;DR: The effectiveness of intracerebroventricular delivery of recombinant human ASM into ASMKO mice showed that ICV delivery of the enzyme led to widespread distribution of the hydrolase throughout the CNS and a significant reduction in lysosomal accumulation of sphingomyelin was observed throughout the brain and also within the spinal cord and viscera.

TL;DR: The results suggest that the nonclinical safety assessment of novel therapeutics should include the use of specific animal models of disease whenever feasible, and the observed toxicity involves the rapid breakdown of large amounts of sphingomyelin into ceramide and/or other toxic downstream metabolites, which are known signaling molecules with cardiovascular and pro-inflammatory effects.