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Headlines 11 leak occurs is poorly understood. Within the heart, we have shown that calcium leak is caused by the inappropriate arrangement of RyR2 within the cell. This project will determine if a similar mechanism underlies calcium leak in AD. It will also examine whether drugs known to prevent calcium leaks in the heart also work in the brain. Validation of the Time toWalking Independently after Stroke Tool (TWIST) Professor Cathy Stinear, University of Auckland $176,316 Around 10,000 New Zealanders experience stroke each year, and most will have difficulty walking afterwards. Regaining the ability to walk independently can make the difference between returning home or having to move to a rest or nursing home. Patients and whānau/family would like to know whether they will walk independently again and how long this will take. Unfortunately, clinicians' predictions are accurate only about half the time. The TWIST tool predicts both whether and when a patient will walk safely on their own again, with 90% accuracy. This study will validate TWIST so it can be implemented in clinical care. Use of a novel gene switch to refine the application of gene therapy for Huntington's disease Associate Professor Deborah Young, University of Auckland $160,743 Co-funded with the Auckland Medical Research Foundation (AMRF) Gene therapy is beginning to deliver impressive therapeutic benefits for some diseases in humans including those affecting the brain. Associate Professor Deborah Young has developed a novel gene switch for use in gene therapy that harnesses disease-specific signals to switch on and restrict the production of the therapy to sick neurons only at the time of need. This project will test the functionality of the gene switch in driving a therapy to ameliorate the development of neuropathological and behavioural deficits in a preclinical model of Huntington's disease. This research will help facilitate the advancement of gene therapy from the bench to the clinic. Small Project grants Decoding the regulatory activity of disease associated SNPs within the Parkinson’s network using a Massively Parallel Reporter Assay (MPRA) Miss Sophie Farrow, University of Auckland $14,955 Parkinson’s disease is a complex neurodegenerative disorder that affects more than 6.2 million individuals worldwide. 200 genetic mutations have been linked to Parkinson’s disease. However, clinicians and scientists have a limited understanding of how these mutations affect disease development and progression. Miss Sophie Farrow thinks these mutations work together as a network. She will use computational and laboratory techniques to decode this network and how these mutations interact and work together. These findings will help her team determine new ways to treat Parkinson’s disease as well as providing options for personalising the current treatments available. Identification of adhesion molecules metastatic melanoma uses to invade across the brain endothelium Dr Scott Graham, University of Auckland $14,911 Brain metastases are present in the majority of individuals who develop advanced melanoma. They are particularly challenging to treat and associate with worsened clinical outcomes. During the metastatic process, the tumour mass sheds cells into the blood. It is from the blood that these metastatic cells gain entry into the brain and other tissues. Therefore, our goal is to identify how these metastatic cells cross the brain endothelial barrier and gain entry. If this project can identify the molecules involved, it will provide targets to reduce or suppress this devastating process.