The reduction of plasmalogens prior to the onset of symptoms represents a new paradigm for the diagnosis, prevention, and treatment of Alzheimer's disease.
The specific plasmalogen restoration therapy for Alzheimer's disease, developed by MLD, is based on a synthetic plasmalogen precursor composed of naturally occurring metabolites. The drug is converted by the body into a variety of plasmalogen lipid species required by neurons.
Preclinical evaluation of our plasmalogen restoration therapy is nearly complete, and we are scaling up the synthesis to support an FDA IND submission and a Phase I clinical trial. Together with our collaborators, we are in the final stages of planning for trials in patients with mild cognitive impairment.
Alzheimer's-related functions of plasmalogens
If the body cannot produce adequate amounts of plasmalogens, neuronal functions are compromised. This includes membrane fusion, which is required for optimal neurotransmission, as well as activity of enzymes responsible for creating beta amyloid, the main component of amyloid plaques. By augmenting plasmalogen levels, our plasmalogen restoration therapy is designed to increase vesicular fusion (left figure), resulting in increased neurotransmitter release and re-uptake, as well as decrease beta-amyloid by restoring the balance between alpha and gamma secretase activities (right figure).
- In vitro and in vivo plasmalogen replacement evaluations in Rhizomelic chondrodysplasia punctata and Pelizaeus-Merzbacher disease using PPI-1011, an ether lipid plasmalogen precursor. Lipids in Health and Disease. 10(1):182 October 2011.
- Cellular diamine levels in cancer chemoprevention: Modulation by ibuprofen and membrane plasmalogens. Lipids in Health and Disease. 10(1):214. November 2011.
- Targeted Metabolomic Analyses of Cellular Models of Pelizaeus-Merzbacher Disease Reveal Plasmalogen and Myo-Inositol Solute Carrier Dysfunction. Lipids in Health and Disease. 10(1):102-June 2011.
- Oral bioavailability of the ether lipid plasmalogen precursor, PPI-1011, in the rabbit: a new therapeutic strategy for Alzheimer’s disease. Lipids in Health and Disease 2011, 10:227.
- Plasmalogen Deficit: A New and Testable Hypothesis for the Etiology of Alzheimer’s Disease. Chapter from the book Alzheimer's Disease Pathogenesis-Core Concepts, Shifting Paradigms and Therapeutic Targets, Publisher: InTech, Chapters published September 12, 2011.