DP Technology, an „AI for Science“ paradigm-driven company, today announced the nomination of DPT0416, a novel CNS penetrable small molecule targeting Lp-PLA2, as a preclinical candidate for the treatment of Alzheimer’s disease (AD).
AD is the most frequent cause of dementia (60%~70%), affecting approximately 57 million people worldwide. Neurovascular dysfunction is an early and predominant event in AD development, independent of classic amyloid pathology. Lp-PLA2 is a phospholipase secreted primarily by inflammatory cells, including peripheral macrophages and CNS microglia. It hydrolyzes oxidized phospholipids typically on low-density lipoprotein (LDL), producing lysophosphatidylcholine (lysoPC) and other potent proinflammatory factors. LysoPC is a key inflammatory mediator on vascular endothelial cells, causing vascular pathology including vessel leakage and BBB damage. The inhibition of Lp-PLA2 by Rilapladib significantly slowed down AD progression and repaired BBB damage in a Phase IIa trial.
DPT0416 is a novel CNS-penetrable Lp-PLA2 inhibitor, exhibiting higher potency, better ADME and physicochemical properties than Rilapladib. In animal models, DPT0416 showed improvement in BBB integrity and a reduction in brain inflammation. The IND-enabling studies are ongoing.
„Alzheimer’s disease imposes increasing burdens on the world. Approvals of three anti-amyloid ? (A?) antibodies mark a pivotal moment in the fight against AD, but the modest clinical efficacy and side effects highlight the complexity of AD and call for more novel interventions with better efficacy. The future treatment of AD should address multiple aspects of the disease, including anti-oxidants, anti-inflammation, and enhancing brain resilience, among others,“ said Xiaomin Zhang, Head of Drug Discovery at DP Technology. „Targeting Lp-PLA2 is a novel therapy that addresses multiple factors beyond amyloid. Given rilapladib’s positive clinical results, the better molecule DPT0416 is expected to bring more benefits to AD and dementia patients.“
