The Cross-Border Biotech Blog

Biotechnology, Health and Business in Canada, the United States and Worldwide

Friday Science Review: March 9, 2012

An accidental neural theme for this weeks Canadian life science research highlights, beginning with…

…higher-order gyrenphalic non-human primates…

Stroke is currently the second leading cause of death here in the West and might surpass heart disease to become the number one killer. In ischemic stroke, the treatment is focused on restoring the restricted blood flow through the use of surgical or pharmacological removal of the causative blood clot. Ischemia causes neuronal damage through initiation of the ischemic cascade, a series of biochemical events that ultimately leads to neuronal death. A promising therapeutic avenue is therefore to block events in this cascade, thereby eliciting a neuroprotective effect.

However, despite promising data in cell and rodent models, a shocking number – over 100 in fact – experimental approaches have failed to demonstrate a neuroprotective effect in clinical trials. While part of this failure rate can be attributed to the poor selection of candidates to advance (from the >1000 reported pre-clinical experimental approaches), poor pre-clinical studies and poor trial design, it has resulted in a general sentiment that neuroprotection in humans is not possible.

However, research by the Tymianski lab at Toronto Western Hospital Research Institute, reported in Nature should help reinstil some much needed optimism. Rather than a rodent model, Cook and colleagues conducted their study in cynomolgus macaques, a higher-order gyrenphalic non-human primate i.e. an animal that possesses a brain more similar to that of humans. Using two experimental models of ischemia, they demonstrated the neuroprotective ability of a PSD-95 inhibitor using a broad set of measures including MRI assessed infarct volumes, retention of transcriptional ability (normally lost in ischemic cells) and retention of neurological function in neurobehavioral assays.

The target PSD-95 is a synaptic scaffolding protein that links NMDA receptors to neurotoxic signaling pathways and while their peptide based inhibitor Tat-NR2B9c had already been shown to be neuroprotective in rats, it is the first time that neuroprotection has been demonstrated in a species so close in complexity to humans. Hopefully with this model there will finally be a path to clinical success and the long sought-after realization of neuroprotection as a treatment modality for ischemic stroke.

Other publications:

  • Developmental transcriptional networks are required to maintain neuronal subtype identity in the mature nervous system. PLoS Genetics. University of British Columbia
  • Ex vivo and in vivo neuroprotection induced by argon when given after an excitotoxic or ischemic insult. PLoS One. Université Laval

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