Neuroprotectant for Acute Ischemic Stroke

Micellized Free Radical Scavenger Prodrug

Advantage

  • Extends half-life, avoids toxic adverse reaction caused by cellular uptake.
  • Improves neurological deficits and reduces infarct volume.
  • Potentially appreciable for other reperfusion injuries: kidney heart, etc.
  • Concept can be utilized for half-life prolongation of rt-PA.

Background & Technology

Although Mechanical thrombectomy following intravenous rt-PA has extended therapeutic time window after onset of stroke symptom, and is becoming a standard treatment, reperfusion injury caused by inflammatory cytokine increases and reactive-oxygen species (ROS) generation remains a serious problem.  Neuroprotectant has not been approved except free radical scavenger Edaravone only in Japan, which is not effective enough because of low concentration for fear of mitochondrial toxicity.
Present technology is block polymer of hydrophilic PEG and hydrophobic TEMPO polymer, radical scavenger grafted hydrophilic chain.  The polymer forms micelles and prevent TEMPO exposure (Fig.1), then dissociate and activate at low pH condition, in reperfusion region.

0927

 

Data & Publication

Well tolerated dosage of RNP (9 mg/kg, 1 mg/mL solution) was injected into the right common carotid artery by intra-arterial injection 20 minutes after reperfusion in a 60 minutes occlusion rat middle cerebral artery occlusion (MCAO) model.
– RNP reduced ROS, DNA damage and apoptosis in ischemic/peri-infarction area.
– RNP reduced BBB disruption, neurological scale and infarction volume (Fig.2).
Stroke. 2017;48:2238-2247. DOI: 10.1161/STROKEAHA.116.016356.

Patents

WO2009/133647 Registered in US, CA, JP

Researchers

Dr. Aiki Marushima, Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Japan
Dr. Yukio Nagasaki, Faculty of Pure and Applied Sciences, University of Tsukuba, Japan

Expectations

We are seeking a company who are interested in commercializing this technology.  The researchers plan to bring this technology to clinical study with industry partners. We can introduce contract manufacturing organization (CMO) for GMP grade RNP production.

Product No: CD-02888

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