Reports of research work funded by grants prior to 2016

Victoria University of Wellington

Using in vivo live cell imaging to monitor the effects of clozapine, an atypical antipsychotic agent, on immune cell trafficking across the blood brain barrier and microglia activation in the animal model of multiple sclerosis

LK Green
Centre for Biodiscovery

Multiple sclerosis remains an immunological disease devoid of sufficient therapeutic options for the estimated 2.3 million people world-wide living with the symptoms of MS.  Our laboratory continues to study the immune regulatory environment in disease progression that leads to inflammation in the central nervous system and progressive paralysis.  We are particularly interested in repurposing alternative drugs for the treatment of MS and investigating the pathway in which these compounds prevent disease.

Having identified an alternative drug compound with FDA approval, clozapine, we have found that this atypical antipsychotic was capable of lessening MS disease-like symptoms in the animal model by altering the neuroinflammatory environment within the central nervous system.  Specifically, our research suggests that treatment with clozapine modifies the infiltrating macrophages, thus the objective of this project was to further investigate immune cell infiltration at the blood-brain barrier junction where leukocytes gain access to the central nervous system.

In order to study the blood-brain barrier, we required the technical expertise and facility of our colleague Professor Britta Engelhardt of the Theordor Kocher Institute (TKI), Bern, Switzerland.  The TKI is currently the only facility world-wide performing intravital epifluorescence videomicroscopy and 2-photon microscopy of the cervical vertebrae region.  At the time of our pilot study, we faced significant challenges in acquiring ethical approval in Switzerland to administer clozapine and a subsequent unexpected roadblock in establishing this methodology in Wellington.  This experience as a whole has generated a strong relationship and collaboration with our colleagues in Switzerland.  Furthermore, the technology transfer between the two institutes has generated new research avenues and introduced new technological concepts to which we are adapting our current work.  We envisage the outcomes from our new relationship with our colleagues in Switzerland will have a positive impact on the future directions for this study.