POSTED: January 31, 2014

Emerging Company Profile
Zocere: Stepping up in stroke

By Lauren Martz
Staff Writer

Zocere- Stepping up in stroke (BioCentury)(FINAL)_Page_1Zocere Inc. may have found a new way to decrease ischemic brain injury in patients following stroke. The company is developing an injectable, degradation-resistant version of the neuroprotective STEP peptide that could improve patient outcomes when given up to six hours after the event, longer than the lone marketed stroke drug.

Protein tyrosine phosphatase non-receptor type 5 (PTPN5; STEP) is a downstream regulator of the NMDA receptor pathway. Activation of the NMDA receptor following stroke causes activation of p38 mitogen-activated protein kinase (p38 MAPK; MAPK14), excessive nitric oxide (NO) production and a neuronal excitotoxic response that contributes to cell death.

When STEP is activated by the NMDA receptor NR1 and NR2B subtypes, the peptide binds and blocks activation of p38 MAPK to dampen the neuronal excitotoxic response.

STEP is up-regulated following stroke, but Surojit Paul and colleagues found the peptide is quickly phosphorylated and degraded following ischemic injury, allowing the spread of neuronal damage. Paul is associate professor of neurology and neuroscience at the University of New Mexico and inventor of Zocere’s technology.

Paul’s team has designed a STEP-based peptide that resists ubiquitin-dependent proteasomal degradation, penetrates the blood-brain barrier and may have a sustained neuroprotective effect.

Last year, the team reported in The Journal of Neuroscience that intravenous injection of the STEP-derived peptide before, during or up to six hours after ischemic injury decreased brain damage compared with control in a rat model of stroke.

The only approved drug for ischemic stroke, Activase alteplase from Roche’s Genentech Inc. unit, is indicated for use within three hours of stroke in the U.S., and within 4.5 hours of symptom onset in the EU. Activase is a recombinant tissue plasminogen activator (tPA) that targets the stroke-causing blood clot. Boehringer Ingelheim GmbH markets the drug as Actilyse in the EU.

“Despite advances in understanding the pathophysiology of cerebral ischemia, successful treatment remains a major challenge in clinical medicine,” Paul told BioCentury. “Reperfusion with recombinant tissue plasminogen activator remains the only pharmacologic therapy. The development of neuroprotection strategies that amplify the time window for thrombolytic treatment is therefore an important goal.”

STEP-based peptides may protect neurons from damage during both ischemia and reperfusion, as well as increase the treatment window for thrombolytic therapeutic administration, he said.

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