EIP Pharma Announces Presentation of Preclinical Data Demonstrating Effects of p38a Kinase Inhibitor Neflamapimod on the Neurodegenerative Process
CAMBRIDGE, Mass., July 17, 2019 /PRNewswire/ -- EIP Pharma, Inc., a CNS-focused therapeutics company, today announced that new preclinical data regarding neflamapimod were presented at the AAIC 2019 scientific meeting in Los Angeles, CA (July 14-18, 2019).
"The findings add to the growing body of evidence that inhibition of p38 alpha kinase has the potential to reverse synaptic dysfunction and treat the neurodegenerative process," said John Alam, MD, President and CEO of EIP Pharma.
The data were reported in two separate poster presentations at the Developing Topics (late-breaker) session at the meeting:
- Title: #P4-506 Role of p38α MAP kinase in amyloid-β derived diffusible ligand (ADDL) induced dendritic spine loss in hippocampal neurons
Authors: Ladan Amin, PhD1, Nhat Le, PhD1, Robert C.C. Mercer, PhD1, Ursula Germann, PhD2, John Alam, MD2 and David A. Harris, MD PhD1, (1) Boston University School of Medicine (2) EIP Pharma, Inc.
Summary & Conclusions: Neflamapimod reduced Amyloid-β derived diffusible ligand (ADDL)-induced dendritic spine retraction starting at the lowest concentration tested (10 nM) and fully blocked the effect at 50 nM. Consistent with a previous report from the Harris lab (Fang, et al 2018), neflamapimod reduced dendritic spine loss after exposure to purified PrPSc, the infectious form of the prion protein, starting at 25 nM, and fully blocked spine retraction at 100 nM. The authors conclude that the results suggest that Aβ oligomers and PrPSc may trigger overlapping synaptotoxic signaling pathways that have in common activation of p38α MAP kinase.
- Title: #P4-692 Effects of p38α MAP kinase inhibition on the neurodegenerative phenotype of the Ts2 Down Syndrome mouse model
Authors: Ying Jiang, PhD1,2, Philip Stavrides, MS1, Sandipkumar Darji, MS1, Dun-Sheng Yang, PhD1,2, Cynthia Bleiwas, MS1, John Smiley, PhD1,2, Ursula Germann, PhD3, John Alam, MD3 and Ralph Nixon, MD, PhD1,2, (1) Nathan Kline Institute for Psychiatric Research (2) NYU Langone Medical Center (3) EIP Pharma, Inc.
Summary & Conclusions: Ts2 transgenic mice that model Down Syndrome and develop typical Alzheimer's disease pathology or wild-type (WT) mice were treated for 28 days with vehicle or neflamapimod in vehicle starting at 4.7-6.4 months of age, when endosomal pathology is evident and cholinergic neuronal loss is developing in Ts2 mice. At the end of treatment, Rab5 activation, Rab5+ endosome size and the number of neurons staining positive for choline acetyltransferase (ChAT+ neurons; i.e. cholinergic neurons) were assessed by immunohistochemical analyses of the medial septal nucleus of the brain. In the Ts2 mice, treatment with neflamapimod reduced Rab5 activation relative to vehicle-treatment and normalized Rab5+ endosome size (i.e. reversed endosomal pathology). Neflamapimod treatment also restored ChAT+ neuron number and normalized morphology (size) in Ts2 mice. Specifically, the number of ChAT+ neurons by immunohistochemistry was reduced by approximately 30% in the medial septal nucleus in vehicle-treated Ts2 mice relative to WT mice, while similar numbers of ChAT+ neurons were seen in the MSN of wild-type (vehicle or neflamapimod treated) and neflamapimod-treated Ts2 mice. The authors conclude that the findings indicate that p38α antagonism could treat the neurodegenerative process beyond reversing synaptic dysfunction.
Neflamapimod is a brain-penetrant, oral small molecule that inhibits the intra-cellular enzyme p38 MAP kinase alpha (p38α). P38α, which is expressed in neurons under conditions of stress and disease, plays a major role in inflammation-induced synaptic toxicity, leading to impairment of synaptic function. Synaptic dysfunction is known to be a major drive of the deficits in cognitive function that are defining characteristics of many CNS diseases. Neflamapimod is currently being studied in a Phase 2b trial for early Alzheimer's disease; and in separate Phase 2 trials in patients with Huntington's disease who have evidence of cognitive dysfunction and in mild-to-moderate dementia of Lewy bodies.
About EIP Pharma, Inc.
EIP Pharma, Inc. is a private, Cambridge, MA-based company advancing CNS-focused therapeutics to benefit patients with neurodegenerative diseases.
For more information, please visit www.eippharma.com.
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