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Headlines 13 Dr BruceMockett, University of Otago A new peripheral gene therapy approach for treating Alzheimer’s disease $247,501 Diseases of the brain are immensely difficult to treat, in part because many therapeutic drugs are prevented from entering the brain by a protective mechanism known as the blood-brain barrier. One answer may lie in a newly discovered virus that is able to efficiently cross the blood-brain barrier. This study will treat a mouse model of Alzheimer's disease with this new virus, modified to carry the gene for a therapeutic protein and administered intravenously. If successful, this work will reveal a new way of delivering therapies to the brain and a new treatment option for neurodegenerative diseases. Small Project Grants Dr Akshata Anchan, University of Auckland Involvement of brain-metastatic cancers and their extracellular vesicles in invasion across the blood- brain barrier endothelium $15,000 Brain-metastatic cancers are the most aggressive forms of cancers with devastating prognoses. They are created by cancers that travel into the brain from other anatomical sites. To do this, cancer cells must interact with the protective blood-brain barrier, that defends the brain against blood- borne pathogens. We aim to investigate this interaction to discover the key components and entities that allow cancer cells to migrate into the brain. We hope to therefore aid research towards therapy for brain metastases. Dr Teena Gamage, University of Auckland Are fetal neural stem cell-derived extracellular vesicles natural therapeutic candidates for preterm brain injury? $15,000 Babies born prematurely are at risk of life-long brain injuries. Unfortunately, we lack effective therapies and accurate diagnostic markers to ameliorate brain injury and provide early detection, respectively, for babies at risk of injury. Our study will seek to characterise the protein content of extracellular vesicles secreted by fetal neural stem cells to identify potential therapeutic candidates for preterm brain injury. Using the same technology, we will investigate potential diagnostic protein biomarkers isolated from fetal plasma-derived extracellular vesicles collected from our preterm brain injury sheep model. Our study has the potential to improve long-term clinical outcomes for tamariki kokoti tau/preterm babies. Dr Francesc March de Ribot, University of Otago Using amiloride to improve regeneration following brain injury $12,640 Recovering brain function following injury is severely limited by scar tissue. Preventing scarring would allow for greater recovery of brain activity. A key contributor to scarring are cells called pericytes. These cells are recruited to damaged sites in the brain where they accumulate. Their continued presence prevents brain tissue reforming. Research at Otago investigating scarring in the kidney has found that a cost-effective and safe drug called amiloride can markedly reduce scarring. Here, we will test if amiloride can reduce scarring in the brain. If so, we will have a new method to treat scarring, restoring brain function following injury. Dr Ailsa McGregor, University of Otago Caging Lithium: Novel drug delivery systems for treatment of bipolar disorder and other mental health conditions $14,976 Lithium has been used for over 60 years to manage bipolar disorder (BPD, mate rangirua) but has significant shortcomings. Patients taking lithium typically remain symptomatically unwell at least half of the time, experience serious adverse effects with long-term use and require frequent blood monitoring. This proof-of-principle project will develop a new drug delivery strategy for lithium that will produce a quicker response and fewer side effects. Dr Siew Hoong Yip, University of Otago Regulation of body weight by hypothalamic dopaminergic neurons $15,000 Obesity affects around 1 in 3 adults in New Zealand. While widely considered a ‘lifestyle’ or ‘environmental’ condition, among neuroscientists there is now clear understanding that obesity is better considered as a disorder of the brain's control of appetite. We recently made a serendipitous discovery that a population of dopamine neurons are involved in appetite control. Here we aim to address the mechanisms underlying this novel finding to provide a new understanding of body weight regulation, which may explain the neurological cause of obesity.