Drug-Induced Phospholipidosis (DIPL)

GLP validated di-22:6 BMP biomarker in urine to assay

Drug-induced Phospholipidosis or similarly called Parkinsonism (DIPL) is a phospholipid storage disorder characterized by an excessive accumulation of multi-lamellar bodies (myeloid bodies) in cells and tissues. Instead of just morphological changes, patients instead will potentially experience an onslaught of clinical toxicities (such as Parkinson’s symptoms), heart irregularities like QT prolongation, or many more afflictions) due to drugs — and in many cases, from anti-depressive drugs. Because DIPL may be linked to unwanted toxicities, its presence may result in the delay or discontinuation of new drug development of non-clinical/clinical studies. DIPL should be carefully evaluated and interpreted on a case-by-case basis, especially for chronically used drugs.

With our proprietary di-22:6-BMP biomarker, Nextcea distinguishes ourselves by quantitating DIPL through LC-MS methods that are:

Non-invasive (urine)

di-22:6 BMP biomarker excreted from tissues to blood streams and accumulated in urine

Validated biomarker quantitated by LC-MS

Thompson KL, Haskins K, Rosenzweig BA, et al.
Comparison of the diagnostic accuracy of di-22:6-bis(monoacylglycerol) phosphate and other urinary phospholipids for drug-induced phospholipidosis or tissue injury in the rat.
Int J Toxicol. 2012;31(1):14-24. doi:10.1177/1091581811430167

Assay sensitivity 96.7 and assay specificity 100

Hsieh F. Tengstrand E.
Drug-induced phospholipidosis assessment from nonlcinical to clinical studies.
Dokusei Shitsumon-Bako 2015, 17: 24-36

Thompson KL, Zhang J, Stewart S, et al.
Comparison of urinary and serum levels of di-22:6-bis(monoacylglycerol) phosphate as noninvasive biomarkers of phospholipidosis in rats.
Toxicol Lett. 2012;213(2):285-291. doi:10.1016/j.toxlet.2012.07.013

Nextcea aspires to provide regulatory views that answer:

  • How long before the onset of phospholipidosis is induced?
  • How long before toxicity associated with clinical outcome related phospholipidosis?
  • How long recovery takes after dosage is ceased?

di-22:6-BMP Biomarker

Di-docosahexaenoyl (22:6)-BMP

Bis (monoacylglycerol) phosphate (BMP) is a unique lysosomal phospholipid that plays important roles in lysosomal degradation pathways. BMP is increased in the tissues of animals and humans with DIPL and the lysosomal storage disorders. Elevated di-docosahexaenoyl (22:6)-BMP (a unique isoform of BMP) is Nextcea’s proprietary biomarker, and in plasma and urine, a reliable indicator of tissue DIPL for nonclinical and clinical studies.

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View full di-22:6 BMP structure

di-22:6 BMP as a validated biomarker to monitor the onset and time course of DIPL

Nextcea has identified our proprietary di-22:6-BMP biomarker as a validated marker of phospholipidosis, with the onset of DIPL containing elevated levels of di-22:6 BMP in urine.

“The data provide evidence supporting the use of di-22:6-BMP as a urinary biomarker of PLD”

Mesens, et al. Toxicol Pathol. 2012;40(3):491-503.

“cholesterol sorting proteins NPC1 and NPC2, the amiodarone-induced traffic jam is thought to be located at the BMP level demonstrating its role in the mechanism of phospholipidosis-induction and its significance for use as a biomarker

Thompson KL, et al. Int J Toxicol. 2012;31(1):14-24.

Providing validated LC-MS/MS DIPL Biomarker Quantitative Assay to manage uncertainty in drug safety better

Nextcea specializes in DIPL bioassay services for non-clinical and clinical studies. We provide GLP validated bioanalytical LC-MS/MS methods for measurement of non-invasive di-22:6-BMP in animal and human matrices (urine).

  • Non-GLP, GLP Study Sample Analysis
  • Correlate DIPL with PK/PD, TK/TD
  • Nonclinical and clinical studies
  • Validated LC-MS/MS Assays