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Ischemic Stroke

We recognized that endothelin B receptors in the brain are key to its development.

Evidence that a deficiency in endothelin B receptors leads to a poorer outcome and exacerbation of damage to the brain following cerebral ischemia suggests a role of endothelin B receptors in the pathophysiological process of ischemic stroke.

We broke new ground by selectively activating endothelin B receptors with PMZ-1620 to reduce the infarct volume and improve neurological functions following ischemic stroke.

PMZ-1620 is likely to offer significant advantages over existing products because it has been found to have anti-apoptotic, anti-inflammatory, and anti-oxidant activity thereby limiting the death of brain cells. It also promotes the formation of new neurons (neurogenesis) and new blood vessels (angiogenesis).

PMZ-1620 has a high safety profile, and is simply administered as an intravenous bolus injection.

Patents issued in United States, China, European Union and Japan.

Status of Ischemic stroke

Product
Pre-Clinical
Clinical

phase 1

phase 2

phase 3

market

Ischemic stroke (PMZ-1620)

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Publications

  • Joshi, M. D., Oesterling, B. M., Wu, C., Gwizdz, N., Pais, G., Briyal, S., and Gulati, A. (2016) Evaluation of liposomal nanocarriers loaded with ETB receptor agonist, IRL-1620, using cell-based assays. Neuroscience 312, 141-152
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  • Gulati, A. (2016) Endothelin Receptors, Mitochondria and Neurogenesis in Cerebral Ischemia. Curr Neuropharmacol 14, 619-626
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  • Bhalla, S., Leonard, M. G., Briyal, S., and Gulati, A. (2016) Distinct Alteration in Brain Endothelin A and B Receptor Characteristics Following Focal Cerebral Ischemia in Rats. Drug Res (Stuttg) 66, 189-195
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  • Puppala, B., Awan, I., Briyal, S., Mbachu, O., Leonard, M., and Gulati, A. (2015) Ontogeny of endothelin receptors in the brain, heart, and kidneys of neonatal rats. Brain Dev 37, 206-215
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  • Leonard, M. G., Prazad, P., Puppala, B., and Gulati, A. (2015) Selective Endothelin-B Receptor Stimulation Increases Vascular Endothelial Growth Factor in the Rat Brain during Postnatal Development. Drug Res (Stuttg) 65, 607-613
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  • Gulati, A. (2015) Understanding neurogenesis in the adult human brain. Indian J Pharmacol 47, 583-584
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  • Leonard, M. G., and Gulati, A. (2013) Endothelin B receptor agonist, IRL-1620, enhances angiogenesis and neurogenesis following cerebral ischemia in rats. Brain Res 1528, 28-41
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  • Leonard, M. G., Briyal, S., and Gulati, A. (2012) Endothelin B receptor agonist, IRL-1620, provides long-term neuroprotection in cerebral ischemia in rats. Brain Res 1464, 14-23
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  • Leonard, M. G., Briyal, S., and Gulati, A. (2011) Endothelin B receptor agonist, IRL-1620, reduces neurological damage following permanent middle cerebral artery occlusion in rats. Brain Res 1420, 48-58
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  • Briyal, S., Gulati, A., and Gupta, Y. K. (2007) Effect of combination of endothelin receptor antagonist (TAK-044) and aspirin in middle cerebral artery occlusion model of acute ischemic stroke in rats. Methods Find Exp Clin Pharmacol 29, 257-263
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  • Gupta, Y. K., Briyal, S., Sharma, U., Jagannathan, N. R., and Gulati, A. (2005) Effect of endothelin antagonist (TAK-044) on cerebral ischemic volume, oxidative stress markers and neurobehavioral parameters in the middle cerebral artery occlusion model of stroke in rats. Life Sci 77, 15-27
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