Title: Out of the endotoxin box: Rethinking pyrogens and pyrogenicity

Speaker: Dr. Djik Maouyo (Pyrodex, LLC)

Host: Dr. Ten-Tsao Wong

Contact imetdirectorsoffice@umces.edu for meeting information.

Abstract: 

The extensive characterization of pattern recognition receptors and their ligands known as pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) have not significantly changed practices in pharmaceutical microbiology. The use of autoclaves and other sterilization methods has assumed that live microbes pose a threat to therapeutic products. Further, the popularity of endotoxin detection using horseshoe crab blood cell lysates also assumes that all endotoxins or lipopolysaccharides are pyrogenic, and conversely suggests that endotoxins alone can cause fever, sepsis, multiple organ failure or death.

In this seminar, we will show that endotoxins are not all the same: some are pyrogenic and others are not. This pharmacological distinction cannot be made using the current gold standard bacterial endotoxin tests based on the Limulus or Tachypleus amebocyte lysates (LAL or TAL respectively) or their derivatives, recombinant factor C or recombinant cascade reagents (rCR). The right tool to detect clinically relevant endotoxins is the monocyte activation test based on human peripheral blood mononuclear cells (PBMCs). However, PBMC responses to pyrogens are not linear and require new paradigms and algorithms to evaluate contaminant pyrogenicity levels. We will present a new definition of endotoxins related to their pharmacological and clinical relevance, show why the use of the LAL and its derivatives is no longer justifiable; this demonstration will also de facto support strict new policies for the protection of American and Asian horseshoe crabs.

Biosketch of Djikolngar Maouyo, Ph.D.,
Founder, Managing Director and President of PyroDex LLC

Prior to founding PyroDex LLC in February 2017, Dr. Maouyo served as Senior Scientist at Lonza Bioscience in its Walkersville, MD plant for more than 9 years. At Lonza he rebuilt and led R&D teams focusing on rapid microbial detection, including universal bacterial and fungal detection, mycoplasma tests, and endotoxin detection  based on Limulus amebocyte lysates. Before joining Lonza, Dr. Maouyo held faculty positions at the University of Maryland School of Medicine and Johns Hopkins University in Baltimore. These faculty positions followed postdoctoral fellowships at Johns Hopkins University and the University of Montreal and a Ph.D. in biology, with a concentration in integrative animal physiology, at the University of Sherbrooke (Quebec, Canada). Dr. Maouyo contributed to the revision of the European Pharmacopeia chapter on the Monocyte Activation Test as a member of the 2019 European Task Force on the MAT. He is highly respected as a world leader and go-to expert in  Monocyte Activation Test science and technology.