CAMBRIDGE, Mass., July 19, 2017 /PRNewswire/ -- EIP Pharma, LLC (www.eippharma.com) today announced that new mechanism of action data regarding neflamapimod were presented at the AAIC 2017 scientific meeting in London, UK (July 16-20, 2017; https://www.alz.org/aaic/). The data were reported in a Developing Topics (late-breaking) poster presentation:
Title: Antagonism of p38 MAPK Alpha (p38) Reverses APP-Induced Endosomal Abnormalities and Improves Lysosomal Dysfunction in Down Syndrome Fibroblasts.
Authors: Alam J, Jiang Y, and Nixon RA.
In a collaboration between EIP Pharma and the laboratory of Prof. Ralph A. Nixon of NYU Langone Medical Center and the Nathan Kline Institute for Psychiatric Research (Orangeburg, NY), the authors evaluated the effects of in-vitro neflamapimod treatment of Down Syndrome fibroblasts on Amyloid Precursor Protein induced endosomal-lysosomal dysfunction; the physiologic defect that has emerged as a major driver of impaired synaptic plasticity in Alzheimer’s disease (Nixon RA, FASEB Journal, June 2017).
The results showed the known endosomal abnormalities in DS-fibroblasts, which serve as a human in-vitro system for AD pathophysiology (Jiang et al, PNAS, 2010), were reversed with 1, 10 or 50 nM neflamapimod. In addition, neflamapimod treatment demonstrated dose-dependent statistically significant improvement in lysosomal function in DS-fibroblasts. The potency for these pharmacological effects was estimated to be >5-fold lower than the potency of neflamapimod for inhibition of cytokine production, and correlated well with dose/concentration-response seen for episodic memory in the human clinical studies.
The authors conclude: “The findings provide the first evidence that p38 antagonism could be a means to therapeutically target Alzheimer-related endosomal dysfunction. Further, the correlation between in vitro potency of neflamapimod on reversing endolysosomal dysfunction with clinical dose-response suggests that this pharmacological effect, rather than anti-inflammatory activity, may underlie the clinical activity of neflamapimod on episodic memory.”
About neflamapimod (VX-745) and p38 MAPK
Neflamapimod is the international nonproprietary name (INN) for the investigational drug discovered by Vertex Pharmaceuticals that had previously been code designated VX-745. EIP Pharma licensed neflamapimod from Vertex in 2014. Neflamapimod is a brain-penetrant oral small molecule that inhibits the intra-cellular enzyme p38 mitogen activated protein kinase alpha (p38).
In the healthy brain, p38a regulates inflammation through effects on immune cells. In conditions of stress and disease, p38 is also expressed in neurons; where it plays a major role in inflammation and/or amyloid beta induced synaptic toxicity, including the impairment of synaptic plasticity that is a major driver of the development of deficits in learning and memory formation which are defining characteristics of Alzheimer’s disease.
About EIP Pharma LLC
EIP Pharma LLC (www.eippharma.com) is a private R&D stage CNS-focused therapeutics company based in Cambridge, Massachusetts.
SOURCE EIP Pharma, LLC
