| First Author | Fallatah W | Year | 2020 |
| Journal | Dis Model Mech | Volume | 13 |
| Issue | 1 | PubMed ID | 31862688 |
| Mgi Jnum | J:285296 | Mgi Id | MGI:6389509 |
| Doi | 10.1242/dmm.042499 | Citation | Fallatah W, et al. (2019) Oral administration of a synthetic vinyl-ether plasmalogen normalizes open field activity in a mouse model of Rhizomelic chondrodysplasia punctata. Dis Model Mech :dmm042499 |
| abstractText | Rhizomelic chondrodysplasia punctata (RCDP) is a rare genetic disorder caused by mutations in peroxisomal genes essential for plasmalogen biosynthesis. Plasmalogens are a class of membrane glycerophospholipids containing a vinyl-ether linked fatty alcohol at the sn-1 position that affect functions including vesicular transport, membrane protein function and free radical scavenging. A logical rationale for the treatment of RCDP is therefore the therapeutic augmentation of plasmalogens. The objective of this work was to provide a preliminary characterization of a novel vinyl-ether synthetic plasmalogen, PPI-1040, in support of its potential utility as an oral therapeutic option for RCDP. First, wild-type mice were treated with (13)C6-labeled PPI-1040, which showed that the sn-1 vinyl-ether and the sn-3 phosphoethanolamine groups remained intact during digestion and absorption. Next, a 4-week treatment of adult plasmalogen deficient Pex7(hypo/null) mice with PPI-1040 showed normalization of plasmalogen levels in plasma, and variable increases in plasmalogen levels in erythrocytes and peripheral tissues (liver, small intestine, skeletal muscle and heart). Augmentation was not observed in brain, lung and kidney. Functionally, PPI-1040 treatment normalized the hyperactive behavior observed in the Pex7(hypo/null) mice as determined by open field test, with a significant inverse correlation between activity and plasma plasmalogen levels. Parallel treatment with an equal amount of ether plasmalogen precursor PPI-1011 did not effectively augment plasmalogen levels or reduce hyperactivity. Our findings show for the first time that a synthetic vinyl-ether plasmalogen is orally bioavailable, and can improve plasmalogen levels in RCDP mouse model. Further exploration of clinical utility is warranted. |
