NGAL: A Key Biomarker in Drug Development

NGAL-in-drug-development

Establishing the safety profile of new drug candidates remains a major challenge at every stage of the development process. However, it is important to identify failures early on so that resources can be diverted to drugs that are more likely to succeed.

“One of the primary reasons for the attrition of promising therapeutic agents from the drug development pipeline is the observation of treatment-related histologic injury to the kidney in animal toxicology studies.”

Sistare et. al. 2009: Accelerating the Development of Biomarkers for Drug Safety. Institute of Medicine (US) Forum on Drug Discovery, Development, and Translation. Washington (DC): National Academies Press (US); 2009

Traditional methods for studying nephrotoxicity such as creatinine measurement may not be the best available as they can take two to three days and may be unreliable. NGAL (neutrophil gelatinase-associated lipocalin) is a sensitive and fast-acting biomarker for identifying Acute Kidney Injury (AKI). After such injury, NGAL levels rise quickly and markedly in both urine and blood, showing a wide response range in comparison with other proposed biomarkers of kidney injury. Its measurement can detect kidney damage within 2 hours of onset. Furthermore NGAL shows a proportionate response to injury, hence, it can also be used to detect improvements in kidney condition.

“An appropriate preclinical biomarker-based strategy facilitates the selection of drug candidates with an improved kidney safety profile. In particular the utilisation of urinary NGAL in a rat 2-day toxicity study provided a tool for a fast, economical assessment of multiple compounds”

Burt, D et al (2014). Application of Emerging Biomarkers of acute kidney injury in development of kidney-sparing polypeptide-based antibiotics. Drug Chem Toxicol 37(2): 204-212

NGAL is the first kidney injury or toxicity biomarker that can be measured in both humans and all the five standard animal models of basic research, medical research and drug development. The unique range of BioPorto NGAL ELISAs available from Alpha Laboratories includes kits for Mouse, Rat, Dog, Pig, Monkey and Human NGAL.

Furthermore we have recently launched a new ELISA kit that is specifically targets MONOMERIC NGAL in human samples. As it is now known that stressed kidney tubular cells predominantly produce the monomeric form of NGAL, as opposed to the primarily neutrophil derived homodimer, this new assay allows the kidney derived element of the NGAL molecule population to be more specifically targeted, leading to a more accurate assessment of the extent of AKI.

All kits feature: 

  • Sample: Urine, plasma, serum, tissue extracts or culture media
  • Ready-to-use working solutions
  • Up to 40 samples in duplicate
  • Pre-coated 96-well ELISA plate
  • Ready-to-use on standard equipment

 

Find out more about NGAL ELISA kits

 

The applications of BioPorto’s animal NGAL ELISA kits in drug development range from drug discovery to pre-clinical toxicity testing. They can be used in pre-clinical studies to detect rises in NGAL concentrations in urine and blood and hence the extent of renal injury, including nephrotoxic injury.

Safety biomarker

NGAL levels rise from baseline if the kidney is injured.

Efficacy biomarker

NGAL levels fall if kidney damage is treated effectively.

Watch the following NGAL video which explains how the NGAL biomarker is detectable almost as soon as the kidney nephrons are damaged:

Note: The video claims that after AKI, NGAL is released from the distal tubules of the nephron. However, early studies such as Matthaeus et al. (2001)1 and Mishra et al. (2003)2 demonstrated that NGAL was principally upregulated in the proximal tubules of the nephron (and in cultured human proximal tubule epithelial cells) after ischemia. The region of the nephron that releases most NGAL into the urine is thus controversial.

 

About the NGAL Assay

Although NGAL is best known as being a biomarker of acute kidney injury (AKI), and is proving to be of great value in drug development in this context, it is now being implicated in as a key component of a number of other pathways and disease states. These include cancer, inflammation and sepsis.

Our sensitive and reliable ELISA based NGAL assays provide a reliable and sensitive means of measuring NGAL levels in both pharmaceutical and medical research settings.

Read More