NPI-505 Acute Stroke Therapy

There are over 700,000 stroke victims in the US each year. NPI-505 would be given to patients who have recently suffered a stroke, greatly decreasing the damaging effects of ischemia in the brain.

NPI-505, a potent inhibitor of a specific Acid-Sensing Ion Channel (ASIC), blocks calcium toxicity in stroke. The blockade of calcium toxicity by NPI-505 is the most potent yet discovered and is completely independent of Glutamate and NMDA receptors.

References:

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Wang WZ, Chu XP, Li MH, Seeds J, Simon RP, Xiong ZG. Modulation of acid-sensing ion channel currents, acid-induced increase of intracellular Ca2+, and acidosis-mediated neuronal injury by intracellular pH. J Biol Chem. 2006 Sep 29;281(39):29369-78. PubMed Reference

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Pignataro G, Simon RP, Xiong ZG. Prolonged activation of ASIC1a and the time window for neuroprotection in cerebral ischaemia. Brain. 2006 Nov 17; PubMed Reference

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Chu XP, Wemmie JA, Wang WZ, Zhu XM, Saugstad JA, Price MP, Simon RP, Xiong ZG. Subunit-dependent high-affinity zinc inhibition of acid-sensing ion channels. J Neurosci. 2004 Oct 6;24(40):8678-89. PubMed Reference

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Xiong Z, Zhu X, Chu X, Minami M, Hey J, Wemmie JA, Price MP, Welsh MJ, Simon RP. A novel neuroprotective strategy in ischemic brain: blocking calcium permeable acid-sensing ion channels. Cell, 2004 Sep 17;118(6):687-98. PubMed Reference

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Chu XP, Zhu XM, Wei WL, Li GH, Simon RP, MacDonald JF, Xiong ZG. Acidosis decreases low Ca(2+)-induced neuronal excitation by inhibiting the activity of calcium-sensing cation channels in cultured mouse hippocampal neurons. J Physiol. 2003 Jul 15;550(Pt 2):385-99. PubMed Reference

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Chu XP, Miesch J, Johnson M, Root L, Zhu XM, Chen D, Simon RP, Xiong ZG. Proton-gated channels in PC12 cells. J Neurophysiol. 2002 May;87(5):2555-61. PubMed Reference

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