Bis(monoacylglycerol)phosphate as a non-invasive biomarker to monitor the onset and time-course of phospholipidosis with drug-induced toxicities.
BACKGROUND
Drug-induced phospholipidosis (PL) is a phospholipid storage disorder characterized by the accumulation of multi-lamellar bodies (myeloid bodies) in tissues. A major unanswered question is whether PL represents a benign adaptive response, symptom or early event in drug toxicity. The absence of a non-invasive biomarker to monitor tissue PL has made it difficult to determine the prevalence and implications of PL in the clinic. As a result, the interpretation of PL in risk assessment remains uncertain in preclinical and clinical drug development.


METHODS
This review describes the rationale for bis(monoacylglycerol)phosphate (BMP) as a biomarker of PL and explores the potential links between PL and the toxicities of drugs.


RESULTS
The similarities between the hypothesized roles of BMP in PL and Niemann-Pick type C disease are discussed. The potential implications of PL for cellular function are described in the context of drug-induced QT prolongation, myopathy and renal toxicity.


CONCLUSIONS
A specific species of BMP, di-docosahexaenoyl-BMP, should be investigated further as a non-invasive biomarker to monitor the onset and time course of PL and to better understand the functional consequences which could contribute to the toxicities of drugs.
Tengstrand
Elizabeth A
EA
Nextcea, Inc., 600 West Cummings Park, #6375, Woburn, MA 01801, USA.
Miwa
Gerald T
GT
Hsieh
Frank Y
FY
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015195:Drug Design; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008064:Lipidoses / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D008133:Long QT Syndrome / Q000139:chemically induced; D008246:Lysophospholipids / Q000378:metabolism*; D050178:Monoglycerides / Q000378:metabolism*; D052556:Niemann-Pick Disease, Type C / Q000175:diagnosis; D010743:Phospholipids / Q000378:metabolism; D018570:Risk Assessment / Q000379:methods; D013997:Time Factors
D015415:Biomarkers; D008246:Lysophospholipids; D050178:Monoglycerides; D010743:Phospholipids; C012786:bis(monoacylglyceryl)phosphate