LEAD COMPOUND PPI-1011
A plasmalogen phospholipid deficiency (particularly those with polyunsaturated fatty acids at sn-2) has been associated with the presence, severity, and rate of progression of dementia of the Alzheimer’s type, and has been suggested to precede the onset of clinical symptoms. Plasmalogen deficiency is now thought to represent a higher risk of Alzheimer’s than the APOE4 genotype. The plasmalogen content of cell membranes directly correlates with the efficiency of vesicular fusion, which is the process whereby neurotransmitters such as acetylcholine are released.
The prevailing hypothesis is that plasmalogen deficiency is a critical underlying mechanism for both the pathological and clinical manifestations of AD.
Plasmalogens are naturally produced by the body and reach peak levels early in life. As the body ages, plasmalogen levels decline in at least a subset of the population. This is likely the result of age-related decline in peroxisomal output, the subcellular organelle where plasmalogen biosynthetic enzymes are located. Other factors, such as accumulating inflammation, environmental factors, diet, and exercise are also known risk factors for dementia and likely interact with plasmalogen deficiency in driving disease progression. At some point, plasmalogen levels decline to a point that cell membrane structure is sufficiently compromised resulting in impaired vesicular fusion and neurotransmitter release. Eventually this leads to early-stage memory loss and ultimately onset of dementia.
MLD’s plasmalogen augmentation program in Alzheimer’s disease is based on the concept that pharmacologically elevating plasmalogen levels within the body using a synthetic plasmalogen precursor will normalize membrane function resulting in improved neurotransmission, reduced amyloid production, and clinically meaningful improvements in patients with dementia.
PPI-1011 is a first-in-class, synthetic orally bioavailable plasmalogen precursor that is metabolized into active plasmalogens by the body. PPI-1011 augments plasmalogens throughout the body, and has been extensively studied the preclinical level in multiple cell lines and species in vivo.
PPI-1011 was conceived and patented by primary inventor Dr. Amin Khan at Phreedom Pharmaceuticals, a subsidiary of Phenomenome Discoveries Inc, and subsequently assigned to Med-Life Discoveries in 2016.
MLD is currently in the process of GMP manufacturing PPI-1011 with IND-enabling safety/pharmacology studies planned within the year, followed by a Phase IIa efficacy trial in subjects with cognitive impairment.
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