Improvement of Blood Plasmalogens and Clinical Symptoms in Parkinson’s Disease by Oral Administration of Ether Phospholipids: A Preliminary Report

Abstract

Introduction. Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease (AD). With the ageing of population, the frequency of PD is expected to increase dramatically in the coming decades. L-DOPA (1,3,4-dihydroxyalanine) is the most effective drug in the symptomatic treatment of PD. Nonmotor symptoms in PD include sleep problems, depression, and dementia, which are not adequately controlled with dopaminergic therapy. Here, we report the efficacy of oral administration of scallop-derived ether phospholipids to some nonmotor symptoms of PD. Methods. Ten (10) patients received oral administration of 1 mg/day of purified ether phospholipids derived from scallop for 24 weeks. Clinical symptoms and blood tests were checked at 0, 4, 12, 24, and 28 weeks. The blood levels of plasmalogens in patients with PD were compared with those of 39 age-matched normal controls. Results. Initial levels of plasma ethanolamine ether phospholipids in PD and ethanolamine plasmalogen of erythrocyte from PD were lower than those of age-matched normal controls. Oral administration of 1 mg/day of the purified ether phospholipids increased plasma ether phospholipids in PD and increased the relative composition of ether phospholipids of erythrocyte membrane in PD. The levels of ether phospholipids in peripheral blood reached to almost normal levels after 24 weeks. Furthermore, some clinical symptoms of PD improved concomitantly. Conclusion. 1 mg/day of oral administration of purified ether phospholipids derived from scallop can increase ether phospholipids in peripheral blood and concomitantly improve some clinical symptoms of PD.

Plasmalogen-Based Liquid Crystalline Multiphase Structures Involving Docosapentaenoyl Derivatives Inspired by Biological Cubic Membranes

“…Biomedical studies have emphasized that AD patients lose up to 60% of plasmalogens from the brain cell membranes ( Farooqui et al, 1997 ; Su et al, 2019 ). There is rising evidence that phospholipids of the plasmalogen-phosphatidylethanolamine type may provide a novel therapeutic approach to impact the neuronal functions in AD and PD pathologies ( Hossain et al, 2013 ; Yamashita et al, 2015 ; Che et al, 2018 , 2020 ; Mawatari et al, 2020 ). Results from recent clinical trials have shown that PUFA-chain ethanolamine plasmalogens can be 100-fold more powerful in stimulating neuro-repair as compared to the conventional ω-3 PUFA species ( Fujino et al, 2017 ; Fujino et al, 2018 ).…”

Plasmalogens, platelet-activating factor and beyond – Ether lipids in signaling and neurodegeneration

“…Most strikingly, a trial with orally administered plasmalogens purified from scallops reported cognitive improvements in a subgroup of AD patients after multiple stratification of the trial cohort ( Fujino et al, 2017 ). Similarly, a recent publication describes improvements of clinical symptoms in a small group of PD patients after oral intake of an ether lipid mixture ( Mawatari et al, 2020 ). In rats infused with Aβ into the ventricles, oral supplementation with plasmalogens led to enhanced performance in behavioral tests assessing cognition together with correction of different markers of oxidative stress, neuroinflammation and neuropathology ( Yamashita et al, 2017 ; Che et al, 2018b ), which was ascribed to the increased availability of, in particular, DHA-containing species ( Yamashita et al, 2017 ).…”

“…Also less marked than in AD, decreased plasmalogen-derived C16:0 dimethylacetal levels (approximately -20% compared with controls; no other subspecies were measured) were identified in the plasma of PD patients ( Dragonas et al, 2009 ). Adding further evidence, a just published report found the levels of ether lipids with ethanolamine head group to be reduced by about 30% in plasma and erythrocytes of PD patients, although with a relatively low number of samples ( Mawatari et al, 2020 ). A series of papers have also investigated plasmalogens in the context of mouse models of PD.…”

Sulfoquinovosylglyceryl ether, a new group of ether lipids from lake ball‐forming green alga Aegagropilopsis moravica (family Pithophoraceae)

“…[21][22][23][24] Shark liver oil, rich in diacylglyceryl ether, was used as a folk medicine or dietary supplement in Norway, [25] Sweden, [25] Japan, [26] and Cuba, [27] and supplementation of shark liver oil or ether lipids resulted in reduction of radiationinduced sicknesses, tumor suppression, immune stimulation, better vaccination efficiency, increased sperm fertility, improved cognitive functions of patients with AD, and partial alleviation of some clinical symptoms by PD. [7,26,[28][29][30][31][32] Two synthetic plasmalogen precursors PPI-1011 and PPI-1040 (Figure 1) are under development for the treatment of AD, [33] PD, [34] or RCDP. [35] In contrast to the abundance of ether lipids in animals and microorganisms, those from plants are quite limited in number.…”

“…In mammals, deficiencies in ether lipid biosynthesis cause two serious congenital disorders, rhizomelic chondrodysplasia punctata (RCDP) and Zellweger spectrum disorders, and lower ether lipid levels in serum or tissues are associated with a range of neurological and metabolic diseases [21] including Alzheimer's disease (AD), schizophrenia, Parkinson's disease (PD), Down syndrome, Gaucher disease, Niemann‐Pick type C disease, diabetes, cardiovascular disease, and cancer [21–24] . Shark liver oil, rich in diacylglyceryl ether, was used as a folk medicine or dietary supplement in Norway, [25] Sweden, [25] Japan, [26] and Cuba, [27] and supplementation of shark liver oil or ether lipids resulted in reduction of radiation‐induced sicknesses, tumor suppression, immune stimulation, better vaccination efficiency, increased sperm fertility, improved cognitive functions of patients with AD, and partial alleviation of some clinical symptoms by PD [7,26,28–32] . Two synthetic plasmalogen precursors PPI‐1011 and PPI‐1040 (Figure 1) are under development for the treatment of AD, [33] PD, [34] or RCDP [35] …”